川芎嗪对链脲佐菌素诱导2型糖尿病大鼠肾病的治疗作用及机制

 目的 探讨川芎嗪对链脲佐菌素(streptozocin，STZ)诱导2型糖尿病大鼠肾病的治疗作用及机制。方法 SD大鼠70只，随机分为正常组和模型组。除正常组外，其余大鼠均给予高脂-高糖饲料喂养4周，再给予链脲佐菌素（40 mg·kg^-1，ip），72 h后测定空腹血糖，将血糖值大于16.67 mmol·L^-1的大鼠随机分为4组：模型组，二甲双胍组（250 mg·kg^-1），川芎嗪低剂量组（80 mg·kg^-1）和高剂量组（160 mg·kg^-1），连续给药8周。正常对照组和模型组大鼠均灌胃给予等量蒸馏水。实验结束时，测定大鼠胰岛素（Ins）、血糖（FSG）和血脂含量及胰岛素抵抗指数(HOMA-IRI)；测定大鼠尿量、尿蛋白、血尿素氮和血肌酐含量；测定大鼠肾素-血管紧张素(Ang Ⅱ)、P选择素(P-selectin)含量、肾组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。光镜下观察肾脏病理学变化。结果 与模型组比较，二甲双胍和高、低剂量川芎嗪给药8周后，均能明显降低大鼠动态空腹血糖（P

The rapeutic Effects and Mechanisms of Tetramethylpyrazine on Streptozocin-Induced-Nephropathy in Type 2 Diabetic Rats

OBJECTIVE To investigate the therapeutic effects and mechanisms of tetramethylpyrazine (TMP)on streptozocin (STZ)-induced-nephropathy in type 2 diabetic rats. METHODS Seventy SD rats were divided into control group (n=14)and model group (n=56)at random. The model rats were fed on high fat and sugar diets for 4 weeks and then injected STZ 40 mg·kg^-1. After 72 h， the fasting blood glucose (FBG)was measured. Rats with high FBG above 16.67 mmol·L^-1 were randomly divided into four groups model， metformin (Met， 250 mg·kg^-1）and TMP (80，160 mg·kg^-1)groups and continuously treated for 8 weeks， and both the control and model groups were given equal distilled water by intragastric administration. The levels of insulin (Ins)， fasting serum glucose (FSG)， total cholesterol (TC)， low density lipoprotein cholesterol (LDL-C)， triglyceride (TG)， free fatty acids (FFAs)， angiotensin II (Ang II)and P-selectin， blood urea nitrogen (BUN)， creatinine(Cr)， creatinine clearance rate (Ccr)in serum， contents of nitric oxide (NO)and activities of nitric oxide synthetase (NOS)in serum and renal tissues， content of malonaldehyde (MDA)and activity of superoxide dismutase (SOD)in renal tissues， and the insulin resistance index (HOMA-IRI)were measured at the end of the experiment. Besides， the urine volume and urinary protein were also determined. The nephridial tissues of the treated rats were observed under optical microscope. RESULTS Compared with model group， the dynamic FBG and total output of urinary protein were significantly decreased (P