蜕皮甾酮对早期糖尿病肾病大鼠的影响

Effects of ecdysterone on early stage diabetic nephropathy in streptozotocin-induced diabetic rats

目的观察蜕皮甾酮对早期糖尿病肾病大鼠的影响。方法运用链脲佐菌素建立糖尿病大鼠模型,分为4组,糖尿病对照组、贝拉普利(10 mg.kg-1.d-1)组、蜕皮甾酮小剂量(10 mg.kg-1.d-1)组、蜕皮甾酮大剂量(100 mg.kg-1.d-1)组,每组大鼠12只。另设正常对照组,大鼠10只。各种药物均溶于生理盐水,正常对照组和糖尿病对照组给予等容量生理盐水,均灌胃给药6 wk。检测大鼠尿白蛋白肌酐清除率(ACR)、血尿素氮(BUN)和肌酐、体重变化及肾组织结缔组织生长因子(CTGF)和Ⅳ型胶原(ColⅣ)的表达水平。结果 6 wk后,正常对照组大鼠体重增加,糖尿病对照组和贝拉普利组大鼠体重下降,与正常对照组相比差异非常显著(P<0.01);蜕皮甾酮大、小剂量组大鼠体重虽有增长,增长幅度低于正常对照组(P<0.05)。与正常对照组相比,糖尿病对照组ACR、BUN显著增高(P<0.01),贝拉普利组、蜕皮甾酮小剂量组和大剂量组ACR、BUN低于糖尿病对照组(P<0.05)。CTGF和ColⅣ阳性细胞多表达于远曲小管和集合管上皮细胞,糖尿病对照组表达水平明显高于正常对照组(P<0.01),其余3组均低于糖尿病对照组(P<0.01)。结论蜕皮甾酮可改善早期糖尿病肾病大鼠的体重减轻和尿白蛋白排泄,抑制肾脏CTGF和ColⅣ表达、防治肾脏纤维化可能为其机制之一。

AIM To investigate the effects of ecdysterone on early stage diabetic nephropathy in streptozocin（STZ）-induced diabetic rats.METHODS Diabetic rats were randomly divided into 4 groups（n = 12）,diabetic control group,benazepril（10 mg·kg-1·d-1）group,ecdysterone small dose（10 mg·kg-1·d-1）group and ecdysterone large dose（100 mg·kg-1·d-1）group.Meanwhile,a normal control group（n = 10）was set.Rats were respectively treated with benazepril,ecdysterone and equivalent normal saline for 6 weeks.Then the biochemistry indexes of blood and urine samples,the expressions of connective tissue growth factor（CTGF）and collagen type Ⅳ（Col Ⅳ）in kidney were measured.RESULTS The weights of normal control groups increased significantly,while the weights of diabetic control group and benazepril group decreased significantly（P 0.01）.The growth rates of ecdysterone small dose and large dose group were lower than that of normal control group（P 0.05）.Compared with the normal control group,the ACR and BUN of diabetic control group increased significantly（P 0.01）.The ACR and BUN of benazepril group,ecdysterone small dose and large dose group were lower than those of diabetic control group（P 0.05）.Compared with normal control group,the expressions of CTGF and Col Ⅳ increased significantly in diabetic control group（P 0.01）and were higher than those in the other three groups（P 0.01）.CONCLUSION Ecdysterone can improve the lose weight and lower the urinary albumin excretion of early stage diabetic nephropathy in STZ-induced diabetic rats probably through inhibiting the expressions of CTGF and Col Ⅳ.