理中汤干预2型糖尿病模型大鼠肾脏的变化

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

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。

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.