中国组织工程研究 ›› 2019, Vol. 23 ›› Issue (27): 4356-4362.doi: 10.3969/j.issn.2095-4344.1385

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

理中汤干预2型糖尿病模型大鼠肾脏的变化

梁丽嫦1,2,范雅雯1,2,牟  雷1,2,谢  天1,2,江晓兵3,任  辉3,张天奉1   

  1. (1广州中医药大学深圳医院(福田),广东省深圳市  518034;2广州中医药大学,广东省广州市  510405;3广州中医药大学第一附属医院,广东省广州市  510405)
  • 收稿日期:2019-03-30 出版日期:2019-09-28 发布日期:2019-09-28
  • 通讯作者: 张天奉,教授,博士生导师,广州中医药大学深圳医院(福田),广东省深圳市 518034
  • 作者简介:梁丽嫦,女,1989年生,广东省中山市人,汉族,广州中医药大学深圳医院(福田)在读博士,主要从事中医药治疗老年性疾病的研究。
  • 基金资助:

    国家自然科学基金(81774338),项目负责人:江晓兵;广东省中医药局项目(20184018),项目负责人:张天奉;深圳市卫计委科研项目(SZXJ2017071),项目负责人:张天奉;深圳市福田区科技局科研项目(FTWS2017002),项目负责人:张天奉

Changes of kidney in rat models of type 2 diabetes mellitus after administering Lizhong Decoction

Liang Lichang1, 2, Fan Yawen1, 2, Mu Lei1, 2, Xie Tian1, 2, Jiang Xiaobing3, Ren Hui3, Zhang Tianfeng1   

  1.  (1Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen 518034, Guangdong Province, China; 2Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; 3the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China)
  • Received:2019-03-30 Online:2019-09-28 Published:2019-09-28
  • Contact: Zhang Tianfeng, Professor, Doctoral supervisor, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen 518034, Guangdong Province, China
  • About author:Liang Lichang, Doctoral candidate, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen 518034, Guangdong Province, China; Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81774338 (to JXB); the Project of Traditional Chinese Medicine Bureau of Guangdong Province, No. 20184018 (to ZTF); the Research Project of Shenzhen Health and Family Planning Commission, No. SZXJ2017071 (to ZTF); the Research Project of Futian District Science and Technology Bureau of Shenzhen, No. FTWS2017002 (to ZTF)

摘要:

文章快速阅读:

文题释义:

2型糖尿病大鼠模型:主要包括自发性动物模型、转基因动物模型和实验性动物模型三大类,考虑到动物来源和成本问题,目前实验性2型糖尿病大鼠模型更为常用。实验性模型是先通过高糖高脂饮食诱导大鼠产生胰岛素抵抗,再联合注射小剂量链脲佐菌素损伤胰岛功能,继而引起血糖升高。该模型可成功模拟人类2型糖尿病的发病过程和代谢特征,因此已被广泛应用于2型糖尿病的发病机制和治疗研究中。
糖尿病肾病:是由糖尿病引起的以慢性高血糖和蛋白尿为主要临床表现的糖尿病微血管并发症。1型糖尿病患者发生糖尿病肾病一般在糖尿病起病5年以上,而2型糖尿病患者发生糖尿病肾病的时间则在确诊糖尿病时即可出现,这与2型糖尿病患者的发病年龄大并且常合并多种其他基础疾病有关。
摘要
背景:
理中汤是临床治疗糖尿病肾病的常用方,但理中汤对糖尿病肾病防治作用的机制尚不明确。
目的:通过观察理中汤对2型糖尿病大鼠肾功能、肾组织形态及肾皮质血管内皮生长因子A、转化生长因子β1、Ⅰ型胶原蛋白表达的影响,验证理中汤对2型糖尿病大鼠有肾保护作用并探讨其作用机制。
方法:SPF级七八周龄SD雄性大鼠60只,购于广州中医药大学实验动物中心[SCXK(粤)2013-0034]。实验方案经广州中医药大学第一附属医院动物实验伦理委员会批准。将大鼠分为空白组和造模组,其中造模组大鼠给予高糖高脂饮食配方诱导大鼠产生食源性肥胖。符合食源性肥胖的大鼠一次性注射小剂量链脲佐菌素(28 mg/kg),连续观察4周,空腹血糖≥11.1 mmol/L纳入为2型糖尿病大鼠。然后再将糖尿病大鼠分为模型组、沙坦组和理中组,连续给药12周。观察每组各项肾脏相关的生化指标、肾脏组织形态学变化和肾皮质血管内皮生长因子A、转化生长因子β1、Ⅰ型胶原蛋白表达。
结果与结论:①理中组肾脏质量指数明显低于模型组(P < 0.05);②理中组的空腹血糖、总胆固醇、三酰甘油、血肌酐、尿素氮、胰岛素、胰岛素抵抗指数、糖化血红蛋白、尿微量白蛋白明显低于模型组(P < 0.05);③理中组大鼠肾组织病理学变化较模型组明显减轻,PAS、PASM和MASSON染色阳性物质染色面积均小于模型组(P < 0.05);④理中组大鼠肾皮质血管内皮生长因子A、转化生长因子β1、Ⅰ型胶原蛋白表达明显低于模型组(P < 0.05);⑤结果表明,理中汤对2型糖尿病大鼠有肾保护作用,其作用机制可能与降糖、降脂和下调血管内皮生长因子A、转化生长因子β1、Ⅰ型胶原蛋白表达有关。

关键词: 理中汤, 2型糖尿病, 糖尿病肾病, 血管内皮生长因子A, 转化生长因子β1, COL-I, 国家自然科学基金

Abstract:

BACKGROUND: Lizhong Decoction is a common prescription for treating diabetic nephropathy. However, the mechanism of Lizhong Decoction on the prevention and treatment of diabetic nephropathy is still unclear.
OBJECTIVE: To confirm that Lizhong Decoction has renal protective effect on type 2 diabetic rats and the underlying mechanism by exploring the changes of renal function, renal tissue morphology and expression of renal cortex vascular endothelial growth factor, transforming growth factor-β1, and type I collagen proteins.
METHODS: Sixty 7-8-week-old male Sprague-Dawley rats, SPF level, were provided by Laboratory Animal Center of Guangzhou University of Chinese Medicine (license No: SCXK2013-0034), and the study was approved by the Experimental Animal Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The rats were divided into control and modeling group. Rats in the modeling group were given high-sugar and high-fat diet to induce diet-induced obesity. These rats were then injected with low-dose streptozotocin (28 mg/kg), and observed for 4 consecutive weeks, and fasting blood glucose ≥ 11.1 mmol/L was included in type 2 diabetic rats. Afterwards, the diabetic rats were divided into model, chatain and Lizhong groups, and were administered for 12 consecutive weeks. The renal biochemical parameters, renal histomorphological changes and expression of renal cortex vascular endothelial growth factor A, transforming growth factor-β1, and type I collagen proteins were detected.
RESULTS AND CONCLUSION: (1) The kidney weight index in the Lizhong group was significantly lower than that in the model group (P < 0.05). (2) The fasting blood glucose, total cholesterol, triglyceride, serum creatinine, urea nitrogen, insulin, insulin resistance index, glycosylated hemoglobin, and urinary microalbumin in the Lizhong group were significantly lower than those in the model group (P < 0.05). (3) The pathological changes of renal tissue in the Lizhong group were significantly reduced compared with the model group. The staining area of PAS, PASM and MASSON staining positive substances in the Lizhong group were all smaller than those in the model group (P < 0.05). (4) The expression levels of vascular endothelial growth factor A, transforming growth factor-β1, and type I collagen proteins in renal cortex in the Lizhong group were significantly lower than those in the model group (P < 0.05). (5) These results indicate that Lizhong Decoction has renal protective effect on type 2 diabetic rats, and its mechanism may be related to reduction in the glucose and lipid and down-regulated expression of vascular endothelial growth factor A, transforming growth factor-β1, and type I collagen proteins.

Key words: Lizhong Decoction, type 2 diabetes, diabetic nephropathy, vascular endothelial growth factor A, transforming growth factor-β1, type I collagen, the National Natural Science Foundation of China

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