摘要
目的:观察丹参多酚酸对2型糖尿病肾病大鼠肾脏的保护作用及其对肾组织ERK1/2表达的影响。方法:50只SD大鼠,随机分为正常组、糖尿病模型组,丹参多酚酸低剂量、中剂量以及高剂量药物干预组,每组10只。采用高脂高糖饮食+一次性腹腔注射链脲佐菌素(STZ)55 mg/kg建立2型糖尿病肾病大鼠模型;丹参多酚酸3个剂量组给予丹参多酚酸10、20、40 mg/kg·d^(-1)注射;8周后处死大鼠,检测24 h蛋白尿,血糖、胰岛素、肌酐及肾脏肥大指数;HE染色观察肾脏病理学变化;同时免疫组化法、Western blot、半定量PCR检测肾组织ERK1/2蛋白及mRNA的表达。结果:与正常组相比,模型组大鼠血糖、24 h蛋白尿、SCr以及肾脏肥大指数明显增加(P<0.05),胰岛素则明显降低(P<0.05);丹参多酚酸高剂量组血糖水平明显低于模型组(P<0.05),胰岛素水平高于模型组(P<0.05);SCr、24小时尿蛋白总量以及肾脏肥大指数,丹参多酚酸3个剂量组明显低于模型组(P<0.05),且改变趋势有明显的剂量依赖性。肾组织HE染色可见,正常组大鼠形态和结构均完整,没有炎症反应;模型组则可见明显的肾小球肥大,同时伴有轻微的系膜轻度增生,肾间质区可见有稍许的炎性细胞浸润;丹参多酚酸3个剂量组相较于模型组上述情况均有一定的好转。免疫组化、Western blot以及RT-PCR结果显示,模型组肾组织ERK1/2蛋白表达较正常组明显升高(P<0.05),而丹参多酚酸组蛋白表达明显降低(P<0.05),高剂量组作用更为明显。结论:丹参多酚酸可明显改善2型糖尿病大鼠肾功能,降低肾脏肥大指数,与其可以降低ERK1/2的表达有关。
Objective： To observe the protective effect of Salvianolic acid on kidney of type 2 diabetic nephropathy rats and influence on ERK1/2 expression on renal tissue, to provide a theoretical basis for the development of polyphenolic acid. Methods： 50 male SD rats were randomly divided into normal group, diabetic model group, low dose, medium dose and high dose Salvianolic acid intervention group. DN models were established by highfat and high -sugar diet（ one months）and one -time intraperitoneal injection of streptozotocin （STZ） 55 mg/kg. After model being built, three dose of Salvianolic acid groups were respectively given Salvianolic acid 10, 20, 40 mg/kg · d-1 for 8 weeks; rats were sacrificed, blood glucose, insulin, creatinine and kidney hyper- trophy were observed. Renal pathologic changes were observed by HE staining. Immunohistochemistry and West- ern blot were used to detect ERK1/2 protein and mRNA expression on renal tissue. Results： Compared with the normal group, the blood glucose, 24 hours proteinuria, SCr and renal hypertrophy index of the model group were significantly increased （ P 〈 0.05 ）, the insulin was significantly decreased （ P 〈 0.05 ） ; the blood glucose and the total amount of urinary protein and the effect of renal hypertrophy in Salvianolic acid high dose group were significantly lower than those in the model group （ P 〈 0. 05 ）, and the change trend was significantly dose - de- pendent. Renal tissue HE staining showed that the morphology and structure of the normal group were complete, and there was no inflammatory reaction, but in the model group had obvious glomerular hypertrophy, accompanied by mild mesangial mild hyperplasia, while the renal interstitial area could be seen a little inflammatory cell in- filtration, compared to the model group, above the situation in Salvianolic acid three dose groups were alleviated （ P 〈 0.05 ）. Compared with the normal group, the ex- pression of ERK1/2 protein in the model group was significantly higher t （P 〈 0. 05 ）, and the expression of ERK1/2 protein in Salvianolic acid three dose groups was significantly decreased （P 〈 0. 05）, especially in the high dose group, the effect was the most obvious. Conclusion： Salvianolic acid can significantly improve renal function and reduce renal hypertrophy index in diabetic rats, which may be related to the decreasing of the ERK1/2 expression.
作者
王玲
吴秋枫
WANG Ling, WU Qiufeng(Tianyou Hospital Affiliated to Wuhan Science and Technology University, Wuhan, Hubei 43006)
出处
《中国中医药科技》
CAS
2018年第2期197-201,共5页
Chinese Journal of Traditional Medical Science and Technology
基金
湖北省科技厅资助项目(2015CFC187)
