Analysis of Kidney Differential Metabolites and Hypoxia Adaptation Mechanism of Plateau Pikas Based on UHPLC-QE-MS

doi:10.12300/j.issn.1674-5817.2024.095

Abstract

Abstract:

Objective To explore the potential mechanisms of hypoxic adaptive metabolic changes in the kidneys of plateau pikas at different altitudes using non-targeted metabolomics analysis via ultra-high-performance liquid chromatography coupled with quadrupole electrostatic field orbital trap-mass spectrometry (UHPLC-QE-MS). Methods 10 plateau pikas were captured at an altitude of 4 360 m in Xingxiuhai area, Maduo County, Guoluo Tibetan Autonomous Prefecture, Qinghai Province (MD group), and 10 plateau pikas were captured at an altitude of 2 900 m in Menyuan area, Haibei Tibetan Autonomous Prefecture, Qinghai Province (MY group). After anesthesia, serum samples were collected, and kidney samples were collected after euthanasia. General physiological and biochemical indicators were measured and metabolomics analysis was performed. Part of the serum samples was used for hematology analysis, another part for blood gas analysis, and the remaining part for biochemical indicator detection. Metabolites were extracted from the kidney tissue samples and then analyzed using UHPLC-QE-MS. Differential metabolites were analyzed using metabolomics principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), with screening criteria set as variable importance in projection (VIP)>1.5 and fold change (FC)>1.5, or VIP>1.5 and FC<1/1.5. Correlation analysis heatmaps, significance analysis volcano plots, signaling pathway recognition bubble charts, and rectangular graphs were used for the analysis of differential metabolites and related signaling pathways. Results The red blood cell count, glucose, urea nitrogen, uric acid, and homocysteine levels in the MD group plateau pikas were higher than those in the MY group, while hemoglobin, hematocrit, creatinine, and carbon dioxide combining power were lower than those in the MY group. This indicated a significant difference in the blood oxygen-carrying capacity of plateau pikas at different altitudes. The principal component pattern recognition analyses, and OPLS-DA permutation test showed that the kidney metabolites of the MD and MY groups of plateau pikas had distinct clustering distributions (R2Y=0.930, Q2=0.655). According to the screening criteria and database comparison, 46 differential metabolites were identified in the kidneys of plateau pikas at different altitudes. In the MD group of plateau pikas, the expression levels of bufadienolide, adenosine, adenine, diosgenin, berberine chloride, carnosol, and astaxanthin were significantly increased (VIP>1.5, P<0.05), while the levels of arachidonic acid, histamine, and coumarin were significantly decreased (VIP>1.5, P<0.05). The analysis of related signaling pathways showed that the biosynthetic pathways of valine, leucine, and isoleucine had the largest impact factors (P<0.05), while the biosynthetic pathways of pantothenate and coenzyme A showed the most significant enrichment (P<0.05). Conclusion The differential metabolites of amino acids, pantothenate, and coenzyme A pathways in the kidneys of plateau pikas at different altitudes may be involved in the metabolic mechanisms of plateau pikas' hypoxia adaptation in high-altitude environments.

Key words: High-altitude hypoxia, Plateau pika, Kidney, UHPLC-QE-MS, Metabolic pathway

CLC Number:

Q95-33

HE Yuxin,BAI Zhenzhong,XUE Hua,et al. Analysis of Kidney Differential Metabolites and Hypoxia Adaptation Mechanism of Plateau Pikas Based on UHPLC-QE-MS[J]. Laboratory Animal and Comparative Medicine, 2025, 45(1): 3-12. DOI: 10.12300/j.issn.1674-5817.2024.095.

Figures/Tables 4

References 20

1	高聪慧, 李吉梅, 徐波, 等. 高原鼢鼠和高原鼠兔血液参数和血红蛋白亚型对不同海拔生境的响应[J]. 生理学报, 2023, 75(1):69-81. DOI: 10.13294/j.aps.2022.0105 .
	GAO C H, LI J M, XU B, et al. Responses of blood parameters and hemoglobin subtypes in plateau zokors and plateau pikas to different altitude habitats[J]. Acta Physiol Sin, 2023, 75(1):69-81. DOI: 10.13294/j.aps.2022.0105 .
2	敖强国, 宋世涛, 邹慧. 高原低压低氧环境对平原健康男青年血像和肾功能影响[J]. 中华保健医学杂志, 2011, 13(6):456-458. DOI: 10.3969/j.issn.1674-3245.2011.06.009 .
	AO Q G, SONG S T, ZOU H. Impact of hypoxia environment at plateau on renal function among healthy male youth[J]. Chin J Health Care Med, 2011, 13(6):456-458. DOI: 10.3969/j.issn.1674-3245.2011.06.009 .
3	刘忠浩, 郭松长, 白祥慧, 等. 低氧暴露下高原鼠兔血液中三种内源性气体分子含量的变化[J]. 基因组学与应用生物学, 2021, 40(4):1539-1543. DOI: 10.13417/j.gab.040.001539 .
	LIU Z H, GUO S C, BAI X H, et al. Changes of three endogenous gas molecules in the blood of plateau pika exposed to hypoxia[J]. Genom Appl Biol, 2021, 40(4):1539-1543. DOI: 10.13417/j.gab.040.001539 .
4	张湑泽, 付林, 邹小艳, 等. 低氧暴露下高原鼠兔肺组织间隙连接蛋白40表达分析[J]. 兽类学报, 2022, 42(5):572-578. DOI: 10.16829/j.slxb.150686 .
	ZHANG X Z, FU L, ZOU X Y, et al. Expression analysis of gap junction protein 40 in lung of plateau pika exposed to hypoxia[J]. Acta Theriol Sin, 2022, 42(5):572-578. DOI: 10.16829/j.slxb.150686 .
5	CHANG Y, ZHANG W, CHEN K, et al. Metabonomics window into plateau hypoxia[J]. J Int Med Res, 2019, 47(11):5441-5452. DOI:10.1177/0300060519879323 .
6	杨卫波, 李素芝, 高钰琪, 等. 急性肾功能损伤在急性高原病发病过程中的差异研究[J]. 第三军医大学学报, 2018, 40(12):1109-1114. DOI: 10.16016/j.1000-5404.201710226 .
	YANG W B, LI S Z, GAO Y Q, et al. Phenotypes of acute renal function injuries in different acute high-altitude diseases[J]. J Third Mil Med Univ, 2018, 40(12):1109-1114. DOI: 10.16016/j.1000-5404.201710226 .
7	BOREA P A, GESSI S, MERIGHI S, et al. Pharmacology of adenosine receptors: the state of the art[J].Physiol Rev, 2018, 98(3): 1591-1625. DOI: 10.1152/physrev.00049.2017 .
8	LI X Y, BERG N K, MILLS T, et al. Adenosine at the interphase of hypoxia and inflammation in lung injury[J]. Front Immunol, 2021, 11:604944. DOI:10.3389/fimmu.2020.604944 .
9	DIAS L, POCHMANN D, LEMOS C, et al. Increased synaptic ATP release and CD73-mediated formation of extracellular adenosine in the control of behavioral and electrophysiological modifications caused by chronic stress[J]. ACS Chem Neurosci, 2023, 14(7):1299-1309. DOI:10.1021/acschemneuro.2c00810 .
10	SEMWAL P, PAINULI S, ABU-IZNEID T, et al. Diosgenin: an updated pharmacological review and therapeutic perspectives[J]. Oxid Med Cell Longev, 2022, 2022:1035441. DOI:10.1155/2022/1035441 .
11	YANG L F, REN S N, XU F, et al. Recent advances in the pharmacological activities of dioscin[J]. Biomed Res Int, 2019, 2019:5763602. DOI:10.1155/2019/5763602 .
12	OCH A, PODGÓRSKI R, NOWAK R. Biological activity of berberine-a summary update[J]. Toxins(Basel), 2020, 12(11):713. DOI:10.3390/toxins12110713 .
13	SHELL B, FAULK K, THOMAS CUNNINGHAM J. Neural control of blood pressure in chronic intermittent hypoxia[J]. Curr Hypertens Rep, 2016, 18(3):19. DOI:10.1007/s11906-016-0627-8 .
14	SATOH T, MCKERCHER S R, LIPTON S A. Nrf2/ARE-mediated antioxidant actions of pro-electrophilic drugs[J]. Free Radic Biol Med, 2013, 65:645-657. DOI:10.1016/j.freeradbiomed. 2013. 07.022 .
15	HASSANEIN E H M, SAYED A M, HUSSEIN O E, et al. Coumarins as modulators of the Keap1/Nrf2/ARE signaling pathway[J]. Oxid Med Cell Longev, 2020, 2020:1675957. DOI:10.1155/2020/1675957 .
16	SUDARIKOVA A V, FOMIN M V, YANKELEVICH I A, et al. The implications of histamine metabolism and signaling in renal function[J]. Physiol Rep, 2021, 9(8): e14845. DOI:10.14814/phy2.14845 .
17	GRANGE C, GURRIERI M, VERTA R, et al. Histamine in the kidneys: what is its role in renal pathophysiology?[J]. Br J Pharmacol, 2020, 177(3):503-515. DOI:10.1111/bph.14619 .
18	喻昌燕, 孟令杰, 姜念, 等. 蟾皮化学成分和药理活性的研究进展[J]. 中草药, 2021, 52(4): 1206-1220. DOI: 10.7501/j.issn.0253-2670.2021.04.035 .
	YU C Y, MENG L J, JIANG N, et al. Research progress on chemical constituents and pharmacological activities of Bofonis Corium[J]. Chin Tradit Herb Drugs, 2021, 52(4):1206-1220. DOI: 10.7501/j.issn.0253-2670.2021.04.035 .
19	UDDIN M N, ALLEN S R, JONES R O, et al. Pathogenesis of pre-eclampsia: marinobufagenin and angiogenic imbalance as biomarkers of the syndrome[J]. Transl Res, 2012, 160(2):99-113. DOI:10.1016/j.trsl.2012.01.005 .
20	CARULLO N, FABIANO G, D'AGOSTINO M, et al. New insights on the role of marinobufagenin from bench to bedside in cardiovascular and kidney diseases[J]. Int J Mol Sci, 2023, 24(13):11186. DOI:10.3390/ijms241311186 .

项目 Item	MD组 MD group (n=10)	MY组 MY group (n=10)	t值 t value	P 值 P value
RBC C_cell/(10¹²·L^-1)	6.93±0.85	6.75±1.65	0.355	0.726
HGB ρ/(g·L^-1)	116.36±7.39	141.40±21.45	-4.074	0.001
HCT φ/(%)	36.45±2.62	42.58±7.09	-2.985	0.007
GLU c/(mmol·L^-1)	6.07±3.66	5.84±2.51	0.177	0.861
BUN c/(mmol·L^-1)	7.48±4.01	5.89±3.00	1.054	0.305
Cr c/(µmol·L^-1)	21.55±5.97	22.36±8.65	-0.258	0.799
UA c/(µmol·L^-1)	45.09±21.90	24.27±15.84	2.555	0.019
CO₂CP c/(mmol·L^-1)	18.72±5.85	26.01±5.83	-2.928	0.008
HCY c/(µmol·L^-1)	25.03±10.31	18.35±12.09	1.393	0.179

项目 Item	MD组 MD group (n=10)	MY组 MY group (n=10)	t值 t value	P 值 P value
RBC C_cell/(10¹²·L^-1)	6.93±0.85	6.75±1.65	0.355	0.726
HGB ρ/(g·L^-1)	116.36±7.39	141.40±21.45	-4.074	0.001
HCT φ/(%)	36.45±2.62	42.58±7.09	-2.985	0.007
GLU c/(mmol·L^-1)	6.07±3.66	5.84±2.51	0.177	0.861
BUN c/(mmol·L^-1)	7.48±4.01	5.89±3.00	1.054	0.305
Cr c/(µmol·L^-1)	21.55±5.97	22.36±8.65	-0.258	0.799
UA c/(µmol·L^-1)	45.09±21.90	24.27±15.84	2.555	0.019
CO₂CP c/(mmol·L^-1)	18.72±5.85	26.01±5.83	-2.928	0.008
HCY c/(µmol·L^-1)	25.03±10.31	18.35±12.09	1.393	0.179

峰值 Peak	代谢物 Metabolites		MD组vs MY组 MD group vs MY group
峰值 Peak	中文名 Chinese name	英文名 English name	RT/s	VIP	P value	FC
4217	蟾蜍二烯羟酸内酯	Bufadienolide	302.521	2.841	0.046 1	216.417
3586	薯蓣皂苷配基	Diosgenin	375.853	2.790	0.000 0	23.644
2596	盐酸小檗碱	Berberine chloride	448.647	1.684	0.010 1	2.418
5668	顺丁烯二酰亚胺	Maleimide	157.759	2.051	0.003 3	2.275
6118	腺嘌呤	Adenine	128.009	1.992	0.002 6	1.355
4040	7,8-脱氢虾青素	7,8-Dehydroastaxanthin	304.975	2.124	0.007 8	13.719
4168	贝那普利酯	Benazeprilat	279.705	2.212	0.000 8	10.772
4196	胆固醇-3,7,12,25-呋喃-3-葡萄糖醛酸	Cholestane-3,7,12,25-tetrol-3-glucuronide	273.513	2.149	0.001 2	5.633
4221	7-乙氧基香豆素	7-Ethoxycoumarin	261.173	1.795	0.017 9	2.839
3212	1-硬脂酰甘油磷酸甘油	1-Stearoylglycerophosphoglycerol	412.530	1.586	0.025 1	2.103
5578	2-甲氧基对乙酰氨基酚硫酸盐	2-Methoxyacetaminophen sulfate	36.282	2.150	0.000 5	0.453
5294	黄嘌呤	Xanthosine	57.261	1.863	0.007 7	0.448
5476	四氢生物蝶呤	Tetrahydrobiopterin	42.319	1.632	0.011 0	0.425
2896	小穗苎麻素	Cryptopleurine	440.968	2.258	0.000 3	0.292
3198	坎二酸	Canbidiolic acid	413.844	2.004	0.012 7	0.284
5570	GDP-3,6-二脱氧-D-半乳糖	GDP-3,6-dideoxy-D-galactose	36.317	1.735	0.001 6	0.197
5501	棉酚	Gossypol	41.544	1.725	0.019 3	0.160
4549	4-香豆素基莽草酸酯	4-Coumaroylshikimate	179.435	2.266	0.009 7	0.103
4596	紫丁香苷	Syringin	169.451	2.374	0.010 3	0.050
5805	5-O-甲基-间氨基-肌醇	5-O-Methyl-myo-inositol	33.358	2.543	0.000 5	0.026
5001	癸二酸	Sebacic acid	135.122	2.295	0.046 3	0.077
4671	萨马素A	Samaderin A	163.209	1.535	0.037 8	0.217
4717	3-脱氢酶	3-Dehydrogenase	157.505	2.158	0.000 9	0.170
4514	硫烯草丹	Sulfallate	185.215	1.844	0.049 0	0.190
5688	双甲苯苄醇	Bitolterol	35.519	1.568	0.001 1	0.271
5523	烟碱	Nicotiamine	169.858	2.201	0.000 1	0.454
7265	吡达隆	Pyridarone	29.322	1.490	0.019 5	0.401
3058	高肌肽	Homocarnosine	412.238	1.966	0.006 3	0.390
3410	阿非迪霉素	Aphidicolin	388.298	2.133	0.005 0	0.205
3101	松香酸盐	Abietate	408.903	2.373	0.033 4	0.088
4573	秦皮苷	Fraxin	174.802	1.098	0.034 3	0.085
3554	高多环内酯	Homodolicholide	380.038	1.667	0.004 0	0.234
3984	法尼基半胱氨酸	Farnesylcysteine	328.343	2.148	0.015 9	0.224
59	泛酸	Pantothenic acid	157.754	2.460	0.000 1	0.480
6640	1-甲基腺苷	1-Methyladenosine	44.286	2.135	0.003 3	0.482
5674	L-二氢脱壳素	L-Dihydroanticapsin	157.754	2.510	0.000 1	0.463
3695	十八碳四烯酸	Stearidonic acid	359.953	2.698	0.003 7	0.103
4631	6-脱氧巴西红厚壳素	6-Deoxyjacareubin	237.103	2.310	0.011 0	0.096
5940	异戊烯焦磷酸	Isopentenyl diphosphate	142.170	2.771	0.038 3	0.004
6407	环氧化物青蒿琥酯	Artomunoxanthentrione epoxide	27.729	2.401	0.000 0	0.249
5768	苄基青霉酸	Benzylpenicilloic acid	151.870	2.655	0.025 4	0.034
302	异亮氨酸	Isoleucine	71.954	1.669	0.045 9	0.698
6496	L-缬氨酸	L-Valine	55.803	1.684	0.018 2	0.637
4165	鼠尾草酚	Carnosol	279.762	2.070	0.003 8	31.391
41	花生四烯酸	Arachidonic acid	466.526	1.614	0.010 5	0.695
5711	组胺	Histamine	35.217	1.740	0.042 9	0.537

峰值 Peak	代谢物 Metabolites		MD组vs MY组 MD group vs MY group
峰值 Peak	中文名 Chinese name	英文名 English name	RT/s	VIP	P value	FC
4217	蟾蜍二烯羟酸内酯	Bufadienolide	302.521	2.841	0.046 1	216.417
3586	薯蓣皂苷配基	Diosgenin	375.853	2.790	0.000 0	23.644
2596	盐酸小檗碱	Berberine chloride	448.647	1.684	0.010 1	2.418
5668	顺丁烯二酰亚胺	Maleimide	157.759	2.051	0.003 3	2.275
6118	腺嘌呤	Adenine	128.009	1.992	0.002 6	1.355
4040	7,8-脱氢虾青素	7,8-Dehydroastaxanthin	304.975	2.124	0.007 8	13.719
4168	贝那普利酯	Benazeprilat	279.705	2.212	0.000 8	10.772
4196	胆固醇-3,7,12,25-呋喃-3-葡萄糖醛酸	Cholestane-3,7,12,25-tetrol-3-glucuronide	273.513	2.149	0.001 2	5.633
4221	7-乙氧基香豆素	7-Ethoxycoumarin	261.173	1.795	0.017 9	2.839
3212	1-硬脂酰甘油磷酸甘油	1-Stearoylglycerophosphoglycerol	412.530	1.586	0.025 1	2.103
5578	2-甲氧基对乙酰氨基酚硫酸盐	2-Methoxyacetaminophen sulfate	36.282	2.150	0.000 5	0.453
5294	黄嘌呤	Xanthosine	57.261	1.863	0.007 7	0.448
5476	四氢生物蝶呤	Tetrahydrobiopterin	42.319	1.632	0.011 0	0.425
2896	小穗苎麻素	Cryptopleurine	440.968	2.258	0.000 3	0.292
3198	坎二酸	Canbidiolic acid	413.844	2.004	0.012 7	0.284
5570	GDP-3,6-二脱氧-D-半乳糖	GDP-3,6-dideoxy-D-galactose	36.317	1.735	0.001 6	0.197
5501	棉酚	Gossypol	41.544	1.725	0.019 3	0.160
4549	4-香豆素基莽草酸酯	4-Coumaroylshikimate	179.435	2.266	0.009 7	0.103
4596	紫丁香苷	Syringin	169.451	2.374	0.010 3	0.050
5805	5-O-甲基-间氨基-肌醇	5-O-Methyl-myo-inositol	33.358	2.543	0.000 5	0.026
5001	癸二酸	Sebacic acid	135.122	2.295	0.046 3	0.077
4671	萨马素A	Samaderin A	163.209	1.535	0.037 8	0.217
4717	3-脱氢酶	3-Dehydrogenase	157.505	2.158	0.000 9	0.170
4514	硫烯草丹	Sulfallate	185.215	1.844	0.049 0	0.190
5688	双甲苯苄醇	Bitolterol	35.519	1.568	0.001 1	0.271
5523	烟碱	Nicotiamine	169.858	2.201	0.000 1	0.454
7265	吡达隆	Pyridarone	29.322	1.490	0.019 5	0.401
3058	高肌肽	Homocarnosine	412.238	1.966	0.006 3	0.390
3410	阿非迪霉素	Aphidicolin	388.298	2.133	0.005 0	0.205
3101	松香酸盐	Abietate	408.903	2.373	0.033 4	0.088
4573	秦皮苷	Fraxin	174.802	1.098	0.034 3	0.085
3554	高多环内酯	Homodolicholide	380.038	1.667	0.004 0	0.234
3984	法尼基半胱氨酸	Farnesylcysteine	328.343	2.148	0.015 9	0.224
59	泛酸	Pantothenic acid	157.754	2.460	0.000 1	0.480
6640	1-甲基腺苷	1-Methyladenosine	44.286	2.135	0.003 3	0.482
5674	L-二氢脱壳素	L-Dihydroanticapsin	157.754	2.510	0.000 1	0.463
3695	十八碳四烯酸	Stearidonic acid	359.953	2.698	0.003 7	0.103
4631	6-脱氧巴西红厚壳素	6-Deoxyjacareubin	237.103	2.310	0.011 0	0.096
5940	异戊烯焦磷酸	Isopentenyl diphosphate	142.170	2.771	0.038 3	0.004
6407	环氧化物青蒿琥酯	Artomunoxanthentrione epoxide	27.729	2.401	0.000 0	0.249
5768	苄基青霉酸	Benzylpenicilloic acid	151.870	2.655	0.025 4	0.034
302	异亮氨酸	Isoleucine	71.954	1.669	0.045 9	0.698
6496	L-缬氨酸	L-Valine	55.803	1.684	0.018 2	0.637
4165	鼠尾草酚	Carnosol	279.762	2.070	0.003 8	31.391
41	花生四烯酸	Arachidonic acid	466.526	1.614	0.010 5	0.695
5711	组胺	Histamine	35.217	1.740	0.042 9	0.537

[1]	ZHANG Naiqun, YUAN Piaopiao, CAO Linrong, YING Na, YANG Taotao. Application of PNR Detection in the Diagnosis and Drug-efficacy Evaluation of Diabetic Kidney Disease in Rats [J]. Laboratory Animal and Comparative Medicine, 2024, 44(5): 543-549.
[2]	Jinxing LIN, Xindong WANG, Xuebing BAI, Liping FENG, Shuwu XIE, Qiusheng CHEN. Fine Structure of the Trunk Kidney and Distribution of Its Secreted Exosomes in the Adult Zebrafish [J]. Laboratory Animal and Comparative Medicine, 2023, 43(5): 531-540.
[3]	Can LAI, Lele LI, Tala HU, Yan MENG. Recent Advances of Animal Models of Renal Interstitial Fibrosis [J]. Laboratory Animal and Comparative Medicine, 2023, 43(2): 163-172.
[4]	Lingqun LU, Honggang GUO, Qiaojuan SHI, Fangwei DAI, Xiaofeng CHU. Histological Characteristics of the Kidney in Mongolian Gerbils of Different Ages [J]. Laboratory Animal and Comparative Medicine, 2023, 43(1): 61-66.
[5]	Xiaoli ZHOU, Qian ZHANG, Zhiyong QIAN. Research Progress on Mechanism and Intervention of Renal Function Injury in Hyperlipidemia Animal Model [J]. Laboratory Animal and Comparative Medicine, 2022, 42(3): 213-219.
[6]	ZHANG Jingyuan, ZHANG Qianqian, ZHAO Yining, YAGN Rong, ZHANG Chengcai, HE Chenjiong, YUAN Zheng, CUI Shufang. Effects of ⁶⁰Co γ-ray Radiation on Kidney, Lung and Skeletal Muscle Tissues of Naked Mole Rats [J]. Laboratory Animal and Comparative Medicine, 2020, 40(6): 513-518.
[7]	SHI Xiang-hua, YANG Wen-bin, XUE Run-miao, ZHAO Jing-yu, XU yan, ZHANG Cai-feng, CHAI Qiu-yan. Effect of Vitamin D₃ on Kidney of Rat at Toxic Dose [J]. Laboratory Animal and Comparative Medicine, 2019, 39(2): 136-139.
[8]	FU Ting-ting, LIU Yan. Pilot Application of Isolated Perfused Chronic Kidney Transgenic Rat Kidney Model for Discovery and Evaluation of Chronic Kidney Disease Drug [J]. Laboratory Animal and Comparative Medicine, 2017, 37(5): 357-362.
[9]	WANG Wen-guang, KUANG De-xuan, YIN Bo-wen, LU Cai-xia, HAN Yuan-yuan, LI Na, TONG Pin-fen, SUN Xiao-mei, CAI Lu-kui, DAI Jie-jie. Study on Infectivity of EV71 in Kidney Cells of Tree Shrew [J]. Laboratory Animal and Comparative Medicine, 2017, 37(2): 123-129.
[10]	ZHOU Wei-min, ZHU Ke-yan, CHEN Fang-ming, CAI Yue-qing, FANG Ming-sun, Qi Yue-han, CHEN min-li. Pathological Change of Kidney in Pkd1 Knock-out Mice with Polycystic Kidney Induced by Tamoxifen [J]. Laboratory Animal and Comparative Medicine, 2017, 37(1): 11-14.
[11]	HUANG Jian-bing, DING Fang-bao, LIU Hao, MEI Ju. Improvement on Kidney Transplantation Model in Mice [J]. Laboratory Animal and Comparative Medicine, 2015, 35(5): 374-377.
[12]	JIANG Yan, WANG Wei, LI Ze-zheng, CHENG Jin, WANG Wei-wei, ZHANG Jin-yuan. Establishment and Evaluation of Acute Kidney Injury Mice Model by Ischemia Reperfusion and Cisplatin Induction [J]. Laboratory Animal and Comparative Medicine, 2014, 34(3): 187-192.
[13]	JIA Lin-chao, LENG Xiao-xia, CHEN Min-li, PAN Yong-ming, SHOU Qi-yang, ZHOU Wei-min, TAO Tao, ZHU Ke-yan. Effect of Anti-aging Tablets on Special Learning Memory and Free Radical Metabolism in Brain of Kidney Deficiency Mouse [J]. Laboratory Animal and Comparative Medicine, 2011, 31(6): 432-435.
[14]	LIN Ruo-qin, FU Xiao-qing, YANG Zhao-yang, ZHU Long, LI Hui-yong. Establishment of Chronic Renal Failure Model in Beagle Dogs by Integrative Operation [J]. Laboratory Animal and Comparative Medicine, 2011, 31(6): 459-461.
[15]	SU Ping, FENG Yang, WU Yu, LIU Zhi-tao, CAI Shi-bin, WANG Ji-hong, DU Yong-hong. Pathobiological Observation on Effect of Melamine on Renal Development in Neonatal Rat [J]. Laboratory Animal and Comparative Medicine, 2011, 31(2): 102-104.