青蒿琥酯对糖尿病肾病大鼠的治疗作用及机制的初探

发布时间：2018-11-05 08:16

【摘要】：目的：观察青蒿琥酯对糖尿病肾病大鼠的治疗作用,并探索其初步的作用机制。方法：雄性SD大鼠采用高糖高脂联合一次性腹腔注射小剂量链脲佐菌素(STZ)法建立2型糖尿病肾病模型,模型成功后随机分为6组：正常对照组(A组)、糖尿病肾病模型组(B组)、青蒿琥酯小剂量组[10mg/(kg/d)] (C组)、青蒿琥酯中剂量组[20mg/(kg/d)] (D组)、青蒿琥酯大剂量组[30mg/(kg/d)] (E组)、依那普利治疗组[10mg/(kg/d)] (F组)。分别干预8周后,检测各组大鼠空腹血糖、体质量、肾脏肥大指数、24小时尿蛋白定量、血肌酐、尿素氮的变化；HE染色光镜下观察肾组织病理形态学变化;ELASIA法检测大鼠肾组织单核细胞趋化蛋白-1 (MCP-1)、肿瘤坏死因子a (TNF-a)的水平；western印迹法检测各组大鼠肾组织中Toll样受体4 (TLR4)表达的变化。结果：模型组大鼠空腹血糖、肾脏肥大指数、24h尿蛋白、血肌酐、尿素氮、肾组织MCP-1、TNF-α、TLR4明显高于正常对照组(P0.01)。各治疗组与模型组比较空腹血糖无明显差异(p0.05),24h尿蛋白、血肌酐、血尿素氮均一定程度下降,差异有统计学意义(P0.01)；青蒿琥酯小剂量组与其大、中剂量组比较差异有统计学意义(p0.01)；但青蒿琥酯大剂量组与依那普利组比较无明显差异(p0.05)。青蒿琥酯能够显著降低肾组织MCP-1、TNF-α、TLR4的含量,其各剂量组与模型组比较,差异有统计学意义(P0.05)；模型组大鼠肾组织见肾小球肥大,系膜区重度增厚,肾间质有炎性细胞浸润,各治疗组上述变化较模型组有所减轻。结论：青蒿琥酯对2型糖尿病肾病具有一定的保护作用,其机制可能部分是通过减轻蛋白尿,减少血肌酐及尿素氮；在蛋白水平上抑制肾组织TLR4的表达；减少炎性因子MCP-1、TNF-α的分泌,抑制肾脏炎症反应,调节肾功能,缓解肾脏的病理损害,从而延缓肾脏病变的发展。
[Abstract]:Aim: to observe the therapeutic effect of artesunate on diabetic nephropathy rats and explore its mechanism. Methods: the male SD rats were randomly divided into 6 groups: normal control group (group A) by intraperitoneal injection of low dose streptozotocin (STZ) with high glucose and high fat, and the model of type 2 diabetic nephropathy was successfully established. Diabetic nephropathy model group (group B), small dose of artesunate [10mg/ (kg/d)] (group C), middle dose group of artesunate [20mg/ (kg/d)] (group D), Artesunate high dose group [30mg/ (kg/d)] (group E), enalapril treatment group [10mg/ (kg/d)] (group F). After 8 weeks of intervention, the changes of fasting blood glucose, body mass, renal hypertrophy index, 24 hour urine protein quantity, serum creatinine and urea nitrogen were measured. The histopathological changes of renal tissue were observed by HE staining, and the levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor a (TNF-a) were detected by ELASIA method. The expression of Toll like receptor 4 (TLR4) was detected by western blot. Results: fasting blood glucose, renal hypertrophy index, 24 hours urine protein, serum creatinine, urea nitrogen, MCP-1,TNF- 伪 and TLR4 were significantly higher in the model group than those in the normal control group (P0.01). There was no significant difference in fasting blood glucose between each treatment group and model group (p0.05). 24 hours urine protein, serum creatinine and blood urea nitrogen were all decreased to a certain extent, the difference was statistically significant (P0.01). There was significant difference between low dose group and middle dose group (p0.01), but there was no significant difference between high dose group and enalapril group (p0.05). Artesunate could significantly reduce the content of MCP-1,TNF- 伪 and TLR4 in renal tissue, and the difference was statistically significant between each dose group and the model group (P0.05). In model group, glomerular hypertrophy, severe thickening of Mesangial area and infiltration of inflammatory cells in renal interstitium were found in the renal tissue of rats. The above changes in each treatment group were less than those in the model group. Conclusion: artesunate has a protective effect on type 2 diabetic nephropathy, which may be partly through reducing proteinuria, reducing serum creatinine and urea nitrogen, and inhibiting the expression of TLR4 in renal tissue at protein level. Reducing the secretion of inflammatory factor MCP-1,TNF- 伪, inhibiting renal inflammation, regulating renal function, alleviating the pathological damage of kidney, thus delaying the development of renal disease.
【学位授予单位】：桂林医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.2

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