川芎嗪对糖尿病大鼠肾保护作用及肾间质结缔组织因子及骨桥蛋白表达的影响

目的 观察川芎嗪对糖尿病大鼠肾保护作用及肾小管间质结缔组织生长因子(CTGF)、骨桥蛋白(OPN)表达水平的影响.方法 选用Wistar大鼠采用一次性腹腔注射链脲佐菌素(STZ)方法诱发糖尿病大鼠模型.成模后随机分为5组,每组12只,分别为模型组、空白对照组、贝那普利组、川芎嗪高、低剂量组,除空白组和模型组外,其余各组按组别分别予贝那普利1.7mg/(kg·d)、川芎嗪150mg、50mg/(kg·d)灌胃,共12周.实验第8周和第12周,测定24h尿蛋白定量;治疗期间检测血糖变化.治疗12周后,检测各组大鼠空腹血糖,全自动生化分析仪检测BUN、Scr.RT-PCR测肾小管间质OPNmRNA表达,免疫组化检测肾小管间质CTGF表达.结果 治疗后,各治疗组与模型组比较,血糖水平均明显下降(P<0.05),以川芎嗪高剂量组最为明显;与正常手术组比较,造模后第8周、第12周模型组尿蛋白明显升高(P<0.05);与模型组比较,各治疗组尿蛋白定量均有下降(P<0.05,P<0.01);治疗各组与模型组血清Scr、BUN比较均显著降低,其中以川芎嗪高剂组下降最为明显(P<0.01);与模型组比较,各药物治疗组大鼠肾间质组织CTGF、OPN表达均明显减少(P<0.05).结论 川芎嗪能通过减少模型大鼠蛋白尿排泄,降低肾间质中CTGF、OPN表达,从而发挥减轻肾间质损害,保护肾功能的作用.

The effect of tetramethylpyrazine on the renoprotection and expression of connective tissue factor and osteopontin in the renal interstitial of diabetic nephropathy rats

Objective To observe the effects of TMP on the renoprotection and expression of connective tissue factor and esteoponfin in the renal interstitial of DN Rats. Methods The DN rats model was established by disposable intraperitoneal injec-tion of STZ on wistar rats. After modeling, randomly divided into model group (n=12), control group (n=12), Benazepril group (n=12) ,high dose TMP group (n=12) and low dose TMP group(n=10). Besides the model and control group the other were re-spectively treat with Benazepril 1.7mg/(kg·d),TMP 150mg/(kg·d) ;TMP 10mg/(kg·d) intragastricall for 12 weeks. The 24h urinary protein count were determined at the 8th,12th week;the change of blood glucose were detected during the treatment period. After 12 weeks,detected the fasting blood glucuse,tbe BUN,SCr were measured by automatic biochemistry analyzer;the expression of OPNmRNA were detected by RT-PCR and the expression of CTGF in renal tubulointerstitial was detected by lmmu-nohistochemistry. Results Compared with the model group,the blood glucose level of each treatment group decreased significant-ly(P<0.05) ,the high dose TMP group was most obvious;compared with the control group,the 24h urinary protein count were sig-nificantly increased it the 8th,12th week(P<0.05) ;compared with the model group,the 24h urinary protein count and the BUN, SCr of each treatment group were decreased at different degree(P<0.05 ,P<0.01) ,the high dose TMP group was most obvious. Compared with the model group, the expression of CTGF,OPN in the renal interstitium of each treatment group were decreased ob-viously(P<0.05). Conclusion the TMP may play a cerlain role in renoprotection and reducing the damage of renal tubulointer-stitial in the DN rats,the mechanism may be through reducing the urine albumium exeretion and downregulating the expression of CTGF,OPN.