SHJH hr 小鼠部分生物学特性及衰老表型的测定与分析

doi:10.12300/j.issn.1674-5817.2022.069

实验动物与比较医学 ›› 2023, Vol. 43 ›› Issue (1): 44-52.DOI: 10.12300/j.issn.1674-5817.2022.069

所属专题：实验动物资源开发与利用

• 实验动物资源开发与利用 • 上一篇下一篇

SHJH ^hr 小鼠部分生物学特性及衰老表型的测定与分析

唐慧青¹(), 常书福², 于志锋³, 张雷³, 谈小倩¹, 瞿伟¹, 李亮¹, 钱珍¹, 顾坚忠¹, 徐平¹()()

^1.上海吉辉实验动物饲养有限公司, 上海 201611
^2.复旦大学附属中山医院, 上海 200032
^3.上海市骨科内植物重点实验室, 上海交通大学医学院附属第九人民医院, 上海 200011

收稿日期:2022-05-23 修回日期:2022-09-21 出版日期:2023-02-25 发布日期:2023-03-09
通讯作者: 徐平（1964—），男，研究员，研究方向：实验动物资源和低温生物学。E-mail： pingxu@jh-labanimal.com。ORCID： 0000-0001-6744-8908
作者简介:唐慧青（1978— ），女，兽医学士，执业兽医师，研究方向：实验动物模型和实验动物疾病。E-mail： tanghuiqing@jh-labanimal.com
基金资助:
上海市科技创新行动计划项目“自发性早衰老小鼠的种群建立及相关机制研究”(21140909100)

Investigation on Biological Characteristics and Aging Phenotype of SHJH ^hr Mice

Huiqing TANG¹(), Shufu CHANG², Zhifeng YU³, Lei ZHANG³, Xiaoqian TAN¹, Wei QU¹, Liang LI¹, Zhen QIAN¹, Jianzhong GU¹, Ping XU¹()()

^1.Shanghai Jihui Laboratory Animal Care Co. , Ltd. , Shanghai 201611, China
^2.Zhongshan Hospital, Fudan University, Shanghai 200032, China
^3.Shanghai Key Laboratory of Orthopaedic Implant, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China

Received:2022-05-23 Revised:2022-09-21 Published:2023-02-25 Online:2023-03-09
Contact: XU Ping (ORCID: 0000-0001-6744-8908), E-mail: pingxu@jh-labanimal.com

摘要/Abstract

摘要：

目的测定与分析SHJH ^hr 小鼠的部分生物学特性及衰老表型，为该小鼠模型用于衰老机制研究、抗衰老药物研发等提供基础数据。方法以对应同周龄段的ICR小鼠为对照，测定SHJH ^hr 小鼠3～16周龄体质量生长数据、1～4胎繁育能力以及生命周期；测定6周龄SHJH ^hr 小鼠的血常规（30项）和血清生化指标（25项）；采集8周龄SHJH ^hr 小鼠静脉血进行流式细胞分析，测定免疫细胞含量；利用显微CT测量4、8、26周龄SHJH ^hr 小鼠松质骨衰老骨结构与骨密度；组织学观察8周龄小鼠骨和关节组织病理学变化。结果与ICR小鼠相比， SHJH ^hr 小鼠16周龄时雌雄体质量均明显偏低（P＜0.05），母鼠繁育性能低下（P＜0.01）或不具备正常的繁育性能。SHJH ^hr 小鼠的生存时间最短57周龄，最长为71周龄，较正常ICR小鼠短，表现出明显的快速衰老现象；同时，部分血液生理生化指标、骨与软骨组织病理变化均显示SHJH ^hr 小鼠生理机能加速衰老与异常。结论 SHJH ^hr 小鼠符合快速衰老的部分特性，并伴有因衰老而导致的某些生理病理变化。

关键词: 自发性快速衰老, 生物学特性, 衰老表型, SHJH ^hr 小鼠

Abstract:

Objective To measure and analyze biological characteristics and aging phenotype of SHJH ^hr mice and provide basic data for the application of the mouse model in aging mechanisms research and antiaging drug development. Methods With ICR mice of the same age as control group, the body mass growth data of SHJH ^hr mice at the age of 3 to 16 weeks, the reproduction ability of 1 to 4 fetuses and the life cycle of SHJH ^hr mice were measured. Blood routine (30 items) and serum biochemical indexes (25 items) of 6-week-old SHJH ^hr mice were measured. The venous blood of 8-week-old SHJH ^hr mice was collected for flow cytometry analysis to determine the content of immune cells. The aging bone structure of the cancellous bone and bone mineral density of SHJH ^hr mice aged 4, 8 and 26 weeks were measured by micro-CT. Histopathological changes of bone and joint of 8-week-old mice were observed. Results Compared with ICR mice, the female and male body mass of SHJH ^hr mice were significantly lower at the age of 16 weeks (P < 0.05), and the reproductive performance of female mice was low (P < 0.01) or did not have normal reproductive capacity. The shortest survival time of SHJH ^hr mice was 57 weeks and the longest was 71 weeks, which was shorter than those of normal ICR mice, showing obvious rapid aging phenomenon. At the same time, some physiological and biochemical indexes of blood and pathological changes of bone and cartilage tissues also showed the accelerated aging and abnormality of animal physiological functions. Conclusion SHJH ^hr mice have some biological characteristics of rapid aging as well as some physiological and pathological changes caused by aging.

Key words: Spontaneous rapid aging, Bio-characteristics, Aging phenotype, SHJH ^hr mice

中图分类号:

Q95-33

唐慧青, 常书福, 于志锋, 张雷, 谈小倩, 瞿伟, 李亮, 钱珍, 顾坚忠, 徐平. SHJH ^hr 小鼠部分生物学特性及衰老表型的测定与分析[J]. 实验动物与比较医学, 2023, 43(1): 44-52.

Huiqing TANG, Shufu CHANG, Zhifeng YU, Lei ZHANG, Xiaoqian TAN, Wei QU, Liang LI, Zhen QIAN, Jianzhong GU, Ping XU. Investigation on Biological Characteristics and Aging Phenotype of SHJH ^hr Mice[J]. Laboratory Animal and Comparative Medicine, 2023, 43(1): 44-52.

图/表 9

参考文献 18

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项目 Item	交配组合 Mating type	第1胎 1st born	第2胎 2nd born	第3胎 3rd born	第4胎 4th born
窝产仔数/只 Litter size, n	对照组（ICR）	15.7±2.4	17.2±1.7	16.8±2.1	15.9±1.9
	hr/hr♂ ×+/hr ♀	16.6±1.9	16.3±2.6	15.8±1.8	16.5±2.2
	+/hr♂ ×hr/hr ♀	14.1±2.1	10.9±1.9^*	8.8±2.9^*	6.1±2.7^**
	hr/hr ♂ ×hr/hr ♀	13.6±2.4	11.5±2.3^*	8.2±3.1^*	7.1±2.8^**
胎间隔 Fetal interval/d	对照组（ICR）	23.4±3.2	28.3±2.7	29.7±2.7	32.2±4.2
	hr/hr♂ ×+/hr ♀	22.9±2.8	30.2±3.1	28.5±4.2	30.9±3.8
	+/hr♂ ×hr/hr ♀	24.5±3.6	42.6±5.7^*	61.1±7.2^**	82.8±35.2^**
	hr/hr♂ ×hr/hr ♀	23.8±3.3	44.2±6.1^*	68.2±12.3^**	87.4±29.9^**
离乳成活率 Survival rate of weaning/%	对照组（ICR）	93.4 (9.34/10)	96.3 (9.63/10)	96.7 (9.67/10)	94.9 (9.49/10)
	hr/hr ♂ ×+/hr ♀	94.2 (9.42/10）	95.6 (9.56/10)	94.8 (9.48/10)	95.1 (9.51/10)
	+/hr♂ ×hr/hr ♀	52.9 (5.29/10)^**	41.2 (4.12/10)^**	32.1 (3.21/10)^**	11.4 (1.14/10)^**
	hr/hr ♂ ×hr/hr ♀	51.4 (5.14/10)^**	42.7 (4.27/10)^**	28.2 (2.82/10)^**	8.7 (0.87/10)^**

项目 Item	交配组合 Mating type	第1胎 1st born	第2胎 2nd born	第3胎 3rd born	第4胎 4th born
窝产仔数/只 Litter size, n	对照组（ICR）	15.7±2.4	17.2±1.7	16.8±2.1	15.9±1.9
	hr/hr♂ ×+/hr ♀	16.6±1.9	16.3±2.6	15.8±1.8	16.5±2.2
	+/hr♂ ×hr/hr ♀	14.1±2.1	10.9±1.9^*	8.8±2.9^*	6.1±2.7^**
	hr/hr ♂ ×hr/hr ♀	13.6±2.4	11.5±2.3^*	8.2±3.1^*	7.1±2.8^**
胎间隔 Fetal interval/d	对照组（ICR）	23.4±3.2	28.3±2.7	29.7±2.7	32.2±4.2
	hr/hr♂ ×+/hr ♀	22.9±2.8	30.2±3.1	28.5±4.2	30.9±3.8
	+/hr♂ ×hr/hr ♀	24.5±3.6	42.6±5.7^*	61.1±7.2^**	82.8±35.2^**
	hr/hr♂ ×hr/hr ♀	23.8±3.3	44.2±6.1^*	68.2±12.3^**	87.4±29.9^**
离乳成活率 Survival rate of weaning/%	对照组（ICR）	93.4 (9.34/10)	96.3 (9.63/10)	96.7 (9.67/10)	94.9 (9.49/10)
	hr/hr ♂ ×+/hr ♀	94.2 (9.42/10）	95.6 (9.56/10)	94.8 (9.48/10)	95.1 (9.51/10)
	+/hr♂ ×hr/hr ♀	52.9 (5.29/10)^**	41.2 (4.12/10)^**	32.1 (3.21/10)^**	11.4 (1.14/10)^**
	hr/hr ♂ ×hr/hr ♀	51.4 (5.14/10)^**	42.7 (4.27/10)^**	28.2 (2.82/10)^**	8.7 (0.87/10)^**

项目 Item	SHJH ^hr 雄鼠 Male SHJH ^hr	ICR 雄鼠 Male ICR	SHJH ^hr 雌鼠 Female SHJH ^hr	ICR 雌鼠 Female ICR
WBC /(10⁹·L^-1)	4.88±1.85	5.80±0.81	5.98±2.64	4.69±1.00
RBC/(10¹²·L^-1)	8.44±0.62	7.78±0.43	8.67±0.61	7.60±0.16
HGB ρ/(g·L^-1)	139.2±6.84	125.5±10.34	147.0±8.29	122.25±1.71
HCT/%	47.64±0.85	41.43±3.20	49.06±1.62	40.33±0.83
MCV/fL	56.68±3.68	53.23±1.37	56.90±4.91	53.08±0.92
MCH m/pg	16.54±0.50	16.12±0.63	16.98±0.51	16.10±0.49
MCHC ρ/(g·L^-1)	292.10±12.77	303.10±4.55	299.90±20.78	303.25±9.54
PLT/(10⁹·L^-1)	1 644.30±131.48	1 526.50±199.58	1 449.60±144.21	1 360.75±81.71
RDW-SD/fL	31.59±2.34	31.67±2.29	32.38±2.03	38.70±2.80
RDW-CV/%	16.86±1.32	17.90±1.72	17.71±1.67	21.51±1.03
PDW/fL	7.18±0.26	7.18±0.32	7.24±0.35	7.20±0.37
MPV/fL	6.91±0.17	7.00±0.24	6.95±0.17	7.11±0.18
P-LCR/%	5.30±0.87	5.80±1.42	5.85±0.87	6.82±0.68
PCT/%	1.14±0.11	1.07±0.11	1.01±0.10	0.97±0.06
NEUT/(10⁹·L^-1)	1.39±0.46	0.97±0.14	2.26±0.87	1.09±0.22
LYMPH/(10⁹·L^-1)	3.38±1.43	4.72±0.71	5.40±2.79	3.50±0.85
MONO/(10⁹·L^-1)	0.03±0.02	0.03±0.01	0.03±0.03	0.01±0.01
EO/(10⁹·L^-1)	0.08±0.04	0.08±0.04	0.28±0.29	0.08±0.03
BASO/(10⁹·L^-1)	0.00±0.00	0.00±0.00	0.00±0.00	0.00±0.00
NEUT/%	29.01±4.43	16.65±1.64	29.68±8.27	23.75±4.65
LYMPH/%	68.66±4.81	81.25±2.19	66.56±7.93	74.18±4.42
MONO/%	0.52±0.30	0.58±0.17	0.41±0.37	0.33±0.10
EO/%	1.81±0.78	1.42±0.66	3.28±2.08	1.63±0.53
BASO/%	0.00±0.00	0.10±0.10	0.07±0.04	0.13±0.15
RET/(10⁹·L^-1)	584.44±157.99	977.67±140.83^*	662.89±190.72	1 562.98±174.91^*
RET/%	7.05±2.28	12.57±1.73^*	7.78±2.62	20.59±2.59^**
LFR/%	52.63±3.37	51.48±3.75	50.66±2.35	44.86±2.94
MFR/%	16.46±1.19	15.03±2.05	15.20±1.40	14.68±0.32
HFR/%	30.91±3.37	33.50±5.41	34.14±2.78	40.45±3.11
IRF/%	47.37±3.37	48.53±3.75	49.34±2.35	55.13±2.94

项目 Item	SHJH ^hr 雄鼠 Male SHJH ^hr	ICR 雄鼠 Male ICR	SHJH ^hr 雌鼠 Female SHJH ^hr	ICR 雌鼠 Female ICR
WBC /(10⁹·L^-1)	4.88±1.85	5.80±0.81	5.98±2.64	4.69±1.00
RBC/(10¹²·L^-1)	8.44±0.62	7.78±0.43	8.67±0.61	7.60±0.16
HGB ρ/(g·L^-1)	139.2±6.84	125.5±10.34	147.0±8.29	122.25±1.71
HCT/%	47.64±0.85	41.43±3.20	49.06±1.62	40.33±0.83
MCV/fL	56.68±3.68	53.23±1.37	56.90±4.91	53.08±0.92
MCH m/pg	16.54±0.50	16.12±0.63	16.98±0.51	16.10±0.49
MCHC ρ/(g·L^-1)	292.10±12.77	303.10±4.55	299.90±20.78	303.25±9.54
PLT/(10⁹·L^-1)	1 644.30±131.48	1 526.50±199.58	1 449.60±144.21	1 360.75±81.71
RDW-SD/fL	31.59±2.34	31.67±2.29	32.38±2.03	38.70±2.80
RDW-CV/%	16.86±1.32	17.90±1.72	17.71±1.67	21.51±1.03
PDW/fL	7.18±0.26	7.18±0.32	7.24±0.35	7.20±0.37
MPV/fL	6.91±0.17	7.00±0.24	6.95±0.17	7.11±0.18
P-LCR/%	5.30±0.87	5.80±1.42	5.85±0.87	6.82±0.68
PCT/%	1.14±0.11	1.07±0.11	1.01±0.10	0.97±0.06
NEUT/(10⁹·L^-1)	1.39±0.46	0.97±0.14	2.26±0.87	1.09±0.22
LYMPH/(10⁹·L^-1)	3.38±1.43	4.72±0.71	5.40±2.79	3.50±0.85
MONO/(10⁹·L^-1)	0.03±0.02	0.03±0.01	0.03±0.03	0.01±0.01
EO/(10⁹·L^-1)	0.08±0.04	0.08±0.04	0.28±0.29	0.08±0.03
BASO/(10⁹·L^-1)	0.00±0.00	0.00±0.00	0.00±0.00	0.00±0.00
NEUT/%	29.01±4.43	16.65±1.64	29.68±8.27	23.75±4.65
LYMPH/%	68.66±4.81	81.25±2.19	66.56±7.93	74.18±4.42
MONO/%	0.52±0.30	0.58±0.17	0.41±0.37	0.33±0.10
EO/%	1.81±0.78	1.42±0.66	3.28±2.08	1.63±0.53
BASO/%	0.00±0.00	0.10±0.10	0.07±0.04	0.13±0.15
RET/(10⁹·L^-1)	584.44±157.99	977.67±140.83^*	662.89±190.72	1 562.98±174.91^*
RET/%	7.05±2.28	12.57±1.73^*	7.78±2.62	20.59±2.59^**
LFR/%	52.63±3.37	51.48±3.75	50.66±2.35	44.86±2.94
MFR/%	16.46±1.19	15.03±2.05	15.20±1.40	14.68±0.32
HFR/%	30.91±3.37	33.50±5.41	34.14±2.78	40.45±3.11
IRF/%	47.37±3.37	48.53±3.75	49.34±2.35	55.13±2.94

项目Item	SHJH ^hr♂	ICR ♂	SHJH^hr ♀	ICR ♀
GPT z/(U·L^-1)	42.63±7.25	34.53±7.97	40.70±9.36	35.30±4.27
GOT z/(U·L^-1)	135.74±51.87	110.95±32.88	154.69±34.67	109.73±25.97
TP ρ//(g·L^-1)	52.82±1.70	47.48±3.21	52.49±3.35	42.64±1.74
ALB ρ//(g·L^-1)	30.30±1.00	28.20±1.85	31.60±2.30	26.21±0.82
GLOB ρ//(g·L^-1)	22.53±0.97	19.29±1.38	20.89±1.93	16.44±0.95
A/G	1.34±0.05	1.46±0.02	1.52±0.15	1.59±0.05
TBIL c/(µmol·L^-1)	0.98±0.33	1.07±0.40	0.47±0.18^*	1.05±0.24
ALP z/(U·L^-1)	188.18±36.13	199.25±50.96	217.22±48.40	191.63±23.97
GLU c/(mmol·L^-1)	6.62±0.64	6.98±1.35	5.49±0.74	6.45±0.52
Urea c/(mmol·L^-1)	9.38±1.57*	6.36±0.52	9.27±1.16^*	6.24±0.61
Crea c/(µmol·L^-1)	11.39±0.96	11.25±1.89	13.77±1.40	13.12±0.90
UA c/(µmol·L^-1)	129.08±21.23	91.65±4.14	112.01±18.22	91.30±5.86
Ca c/(mmol·L^-1)	2.42±0.07	2.59±0.08	2.38±0.05	2.55±0.07
P c/(mmol·L^-1)	2.84±0.35	3.76±0.25	3.43±0.22	3.78±0.22
CHOl c/(mmol·L^-1)	3.55±0.37	3.15±0.48	1.96±0.33	1.98±0.23
TG c/(mmol·L^-1)	2.22±0.70*	1.34±0.34	1.59±0.37*	0.85±0.31
HDL-C/(mmol·L^-1)	2.11±0.19	2.48±0.40	1.35±0.24	1.54±0.19
LDL-C/(mmol·L^-1)	0.23±0.03	0.40±0.04	0.18±0.03	0.27±0.05
CK z/(U·L^-1)	2 780.68±1 965.23	1 838.40±859.10	2 530.90±897.23	1 906.9±846.35
LDH z/(U·L^-1)	1 063.48±155.12	811.95±208.50	930.97±132.80	610.02±177.99
K c/(mmol·L^-1)	6.56±0.38	6.50±0.42	5.97±0.35	5.87±0.23
Na c/(mmol·L^-1)	168.35±2.34	162.78±3.02	167.10±1.97	159.53±1.41
Cl c/(mmol·L^-1)	116.08±3.16	109.47±1.14	118.26±1.72	109.52±0.87
CHE z/(U·L^-1)	7 596.10±1 065.80	6 658.75±172.88	9 730.10±1 555.38	5 431.25±1 050.21
NEFA c/(mmol·L^-1)	1.42±0.24^*	0.94±0.15	1.11±0.16^**	0.60±0.17

SHJH ^hr 小鼠部分生物学特性及衰老表型的测定与分析

Investigation on Biological Characteristics and Aging Phenotype of SHJH ^hr Mice

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SHJH hr 小鼠部分生物学特性及衰老表型的测定与分析

Investigation on Biological Characteristics and Aging Phenotype of SHJH hr Mice

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SHJH ^hr 小鼠部分生物学特性及衰老表型的测定与分析

Investigation on Biological Characteristics and Aging Phenotype of SHJH ^hr Mice