1型糖尿病早期大鼠空肠的神经功能及组织形态学变化

doi:10.12300/j.issn.1674-5817.2020.065

实验动物与比较医学 ›› 2021, Vol. 41 ›› Issue (2): 131-137.DOI: 10.12300/j.issn.1674-5817.2020.065

• 论著:人类疾病动物模型 • 上一篇下一篇

1型糖尿病早期大鼠空肠的神经功能及组织形态学变化

王嫚, 祗明花, 耿旭芳, 佟苗苗, 梁红玉, 赵丁

河北医科大学药学院,石家庄 050017

收稿日期:2020-06-02 修回日期:2020-07-15 出版日期:2021-04-25 发布日期:2021-04-30
作者简介:王嫚(1994—), 女, 硕士, 助理实验师, 从事天然药物抗糖尿病实验研究。E-mail: wangman0319@126.com
基金资助:
河北省重点基础研究项目(17967753D)

Jejunal Nerve Regulation and Histomorphological Changes in Rats with Early Type 1 Diabetes

WANG Man, ZHI Minghua, GENG Xufang, TONG Miaomiao, LIANG Hongyu, ZHAO Ding

School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China

Received:2020-06-02 Revised:2020-07-15 Online:2021-04-25 Published:2021-04-30

摘要/Abstract

摘要： 目的探讨1型糖尿病早期大鼠空肠平滑肌的氮能神经和胆碱能神经功能,以及空肠组织形态学变化。方法将雄性SD大鼠随机分为正常对照组和糖尿病模型组,通过腹腔注射链脲佐菌素（streptozocin,STZ）60 mg/kg建立糖尿病大鼠模型。4周后运用电场刺激诱发神经源性收缩反应,并采用离体器官肌张力分析方法观察离体空肠平滑肌的收缩反应,以及氮能神经和胆碱能神经功能的改变;石蜡组织切片行HE染色及免疫组织化学检测,观察空肠组织形态学变化。结果与正常大鼠相比,STZ诱导的糖尿病早期大鼠的空肠肌间胆碱能神经功能受损,而氮能神经功能未见明显变化;糖尿病大鼠空肠组织绒毛杂乱无序且断裂,肌层增厚,杯状细胞减少,绒毛长度与肠隐窝深度之比（绒腺比）减小。结论在STZ诱导后4周的1型糖尿病早期大鼠模型中,空肠组织的神经功能和形态学均发生了明显变化,提示肠道作为糖尿病敏感器官,在糖尿病早期诊断及预防中具有重要的临床参考意义。

关键词: 糖尿病大鼠, 空肠, 氮能神经, 胆碱能神经, 组织形态学

Abstract: Objective To investigate functional changes of nitrergic and cholinergic nerves in the jejunum smooth muscle, and to observe jejunal histomorphology in rats with early type 1 diabetes. Methods Male Sprague Dawley (SD) rats were randomly divided into a normal control group and a diabetic model group. Rats in the diabetic model group were administered 60 mg/kg streptozotocin (STZ) by intraperitoneal injection. After 4 weeks, neurogenic contractile responses were induced by electric field stimulation, and functional changes in nitrergic and cholinergic nerves were observed in the isolated jejunum of diabetic rats. Histomorphological changes in the jejunum were observed by hematoxylin and eosin staining of paraffin-embedded tissue sections and immunohistochemistry. Results Compared with that in the normal rats, the jejunal intermuscular cholinergic nerve rats with early diabetes was damaged, whereas the nitrogenous nerve did not exhibit a such lesions. The villi of the jejunum were disrupted and disorderly, the muscularis was thickened, goblet cell numbers were decreased, and the ratio of villus length to intestinal crypt depth was diminished in diabetic rats. Conclusion In the early stage (4 weeks) of STZ-induced type 1 diabetes in rats, the neurological function and morphology of jejunal tissues were significantly changed. It suggests that the intestine is a sensitive organ in diabetes and has important clinical implications for the early prevention and detection of diabetes.

Key words: Diabetic rats, Jejunum, Nitrergic nerves, Cholinergic nerves, Histomorphology

中图分类号:

R-332
Q95-33

王嫚, 祗明花, 耿旭芳, 佟苗苗, 梁红玉, 赵丁. 1型糖尿病早期大鼠空肠的神经功能及组织形态学变化[J]. 实验动物与比较医学, 2021, 41(2): 131-137.

WANG Man, ZHI Minghua, GENG Xufang, TONG Miaomiao, LIANG Hongyu, ZHAO Ding. Jejunal Nerve Regulation and Histomorphological Changes in Rats with Early Type 1 Diabetes[J]. Laboratory Animal and Comparative Medicine, 2021, 41(2): 131-137.

图/表 4

参考文献

[1] MALO M S.A high level of intestinal alkaline phosphatase is protective against type 2 diabetes mellitus irrespective of obesity[J]. EBioMedicine, 2015, 2(12): 2016-2023. DOI:10.1016/j.ebiom.2015.11.027.
[2] D'ADDIO F, FIORINA P. Type 1 diabetes and dysfunctional intestinal homeostasis[J]. Trends Endocrinol Metab, 2016, 27(7):493-503. DOI:10.1016/j.tem.2016.04.005.
[3] 张博纶, 李敬林. 从“脾失健运”认识糖尿病肠病病机[J]. 中医药临床杂志, 2016, 28(11): 1532-1533. DOI:10.16448/j.cjtcm.2016.0537.
[4] 张观坡. 谷氨酸兴奋毒性在糖尿病大鼠选择性nNOS神经元减少及胃轻瘫中的作用[D]. 上海: 第二军医大学, 2014.
[5] 王晓青. 糖尿病性胃肠功能紊乱的回顾性分析[D]. 昆明: 昆明医科大学, 2016.
[6] 刘燕平, 范一宏, 吕宾. 肠壁神经丛损伤和修复因素研究进展[J]. 胃肠病学, 2013, 18(5):313-316. DOI:10.3969/j.issn.1008-7125.2013.05.014.
[7] BAGY NSZKI M, B DI N. Diabetes-related alterations in the enteric nervous system and its microenvironment[J]. World J Diabetes, 2012, 3(5):80-93. DOI:10.4239/wjd.v3.i5.80.
[8] BELAI A, LEFEBVRE R A, BURNSTOCK G.Motor activity and neurotransmitter release in the gastric fundus of streptozotocin-diabetic rats[J]. Eur J Pharmacol, 1991, 194(2/3): 225-234. DOI:10.1016/0014-2999(91)90109-4.
[9] 侯宁宁, 王朝迅, 雒瑢, 等. STZ-糖尿病大鼠小肠动力与肠神经胆碱能和氮能神经元关系的研究[J]. 天津医科大学学报, 2007, 13(2): 165-167, 170. DOI:10.3969/j.issn.1006-8147.2007.02.008.
[10] CHAUDHURY A, DE MIRANDA-NETO M H, FERNANDES PEREIRA R V, et al. Myosin Va but not nNOS〈 is significantly reduced in jejunal musculomotor nerve terminals in diabetes mellitus[J]. Front Med (Lausanne), 2014, 1: 17. DOI:10.3389/fmed.2014.00017.
[11] 郝璋森, 梁红玉, 侯聪聪, 等. 1型糖尿病大鼠模型早期胃平滑肌功能的改变研究[J]. 中国比较医学杂志, 2015, 25(11):52-58. DOI:10.3969/j.issn.1671-7856.2015.11.012.
[12] 张远远, 杨志伟. 啮齿类动物糖尿病模型[J]. 中国实验动物学报, 2011, 19(3):269-274. DOI:10.3969/j.issn.1005-4847.2011.03.020.
[13] 陆英杰, 连至诚, 钟毅, 等. 糖尿病30周大鼠胃肌间丛神经元尼氏体的变化[J]. 中国糖尿病杂志, 2010, 18(4):303-305. DOI:10.3969/j.issn.1006-6187.2010.04.020.
[14] 马辉. 凉血愈肠汤对大鼠放射性肠炎肠黏膜修复机制研究[D]. 锦州: 辽宁医学院, 2013.
[15] AFSHIN S, KESHAVARZ M, SALAMI M, et al.Effect of indomethacin on electrical field stimulation-induced contractions of isolated transverse and longitudinal rat gastric fundus strips[J]. World J Gastroenterol, 2005, 11(34): 5358-5361. DOI:10.3748/wjg.v11.i34.5358.
[16] 常兰, 张鹏飞, 陈付菊, 等. 藏羚羊和藏绵羊小肠黏膜结构和黏膜免疫相关细胞的比较[J]. 中国病理生理杂志, 2012, 28(9):1658-1664. DOI:10.3969/j.issn.1000-4718.2012.09.021.
[17] 刘荣莉. 糖尿病肠病[J]. 实用全科医学, 2005, 3(6):488. DOI:10.16766/j.cnki.issn.1674-4152.2005.06.017.
[18] REGALIA J, CAI F, HELKE C.Streptozotocin-induced diabetes and the neurochemistry of vagal afferent neurons[J]. Brain Res, 2002, 938(1-2):7-14. DOI:10.1016/S0006-8993(02)02456-3.
[19] CHANDRASEKHARAN B, SRINIVASAN S.Diabetes and the enteric nervous system[J]. Neurogastroenterol Motil, 2007, 19(12):951-960. DOI:10.1111/j.1365-2982.2007.01023.x.
[20] BACCARI M C, IACOVIELLO C, CALAMAI F.Nitric oxide as modulator of cholinergic neurotransmission in gastric muscle of rabbits[J]. Am J Physiol, 1997, 273(2 Pt 1): G456-G463. DOI:10.1152/ajpgi.1997.273.2.G456.
[21] 张观坡, 高峻, 李桂香, 等. 硫化氢对大鼠肠缺血再灌注后回肠收缩活性的保护作用[J]. 胃肠病学, 2012, 17(2): 119-123. DOI:10.3969/j.issn.1008-7125.2012.02.014.
[22] XUE L, SUZUKI H.Electrical responses of gastric smooth muscles in streptozotocin-induced diabetic rats[J]. Am J Physiol, 1997, 272(1 Pt 1):G77-G83. DOI:10.1152/ajpgi.1997.272.1.g77.
[23] CELLEK S, FOXWELL N A, MONCADA S.Two phases of nitrergic neuropathy in streptozotocin-induced diabetic rats[J]. Diabetes, 2003, 52(9):2353-2362. DOI:10.2337/diabetes.52.9.2353.
[24] IMAEDA K, TAKANO H, KOSHITA M, et al.Electrical properties of colonic smooth muscle in spontaneously non-insulin-dependent diabetic rats[J]. J Smooth Muscle Res, 1998, 34(1):1-11. DOI:10.1540/jsmr.34.1.
[25] BENIAS P C, WELLS R G, SACKEY-ABOAGYE B, et al.Author correction: Structure and distribution of an unrecognized interstitium in human tissues[J]. Sci Rep, 2018, 8: 7610. DOI:10.1038/s41598-018-25732-x.
[26] 董文逍, 曹海龙, 王邦茂. 杯状细胞在肠道疾病发病中作用的研究进展[J]. 国际消化病杂志, 2015, 35(4): 244-246, 269. DOI:10.3969/j.issn.1673-534X.2015.04.005.

1型糖尿病早期大鼠空肠的神经功能及组织形态学变化

Jejunal Nerve Regulation and Histomorphological Changes in Rats with Early Type 1 Diabetes

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 4

参考文献

相关文章 3

编辑推荐

Metrics

本文评价

[1]	王艺, 彭国庆, 江新泉, 董灵芝, 宋文刚, 张秋玲. 两种血糖仪与全自动血生化仪测量糖尿病大鼠血糖的比较[J]. 实验动物与比较医学, 2015, 35(5): 411-413.
[2]	陈立新, 赵先哲, 乔伟伟, 顾坚忠, 王龙霞. 保留不同长度十二指肠的DJB术后GK大鼠肠道激素的研究[J]. 实验动物与比较医学, 2014, 34(3): 223-227.
[3]	胡建石1，黄焱2，林玲1，郑志竑1，陈少强2. 毛细管电泳法检测糖尿病大鼠糖化血红蛋白及其对治疗效果的评价[J]. , 2001, 21(2): 92-97.