【摘要】：目的：觀察青蒿琥酯對糖尿病腎病大鼠的治療作用,并探索其初步的作用機制。方法：雄性SD大鼠采用高糖高脂聯(lián)合一次性腹腔注射小劑量鏈脲佐菌素(STZ)法建立2型糖尿病腎病模型,模型成功后隨機分為6組：正常對照組(A組)、糖尿病腎病模型組(B組)、青蒿琥酯小劑量組[10mg/(kg/d)] (C組)、青蒿琥酯中劑量組[20mg/(kg/d)] (D組)、青蒿琥酯大劑量組[30mg/(kg/d)] (E組)、依那普利治療組[10mg/(kg/d)] (F組)。分別干預(yù)8周后,檢測各組大鼠空腹血糖、體質(zhì)量、腎臟肥大指數(shù)、24小時尿蛋白定量、血肌酐、尿素氮的變化；HE染色光鏡下觀察腎組織病理形態(tài)學(xué)變化;ELASIA法檢測大鼠腎組織單核細(xì)胞趨化蛋白-1 (MCP-1)、腫瘤壞死因子a (TNF-a)的水平；western印跡法檢測各組大鼠腎組織中Toll樣受體4 (TLR4)表達(dá)的變化。結(jié)果：模型組大鼠空腹血糖、腎臟肥大指數(shù)、24h尿蛋白、血肌酐、尿素氮、腎組織MCP-1、TNF-α、TLR4明顯高于正常對照組(P0.01)。各治療組與模型組比較空腹血糖無明顯差異(p0.05),24h尿蛋白、血肌酐、血尿素氮均一定程度下降,差異有統(tǒng)計學(xué)意義(P0.01)；青蒿琥酯小劑量組與其大、中劑量組比較差異有統(tǒng)計學(xué)意義(p0.01)；但青蒿琥酯大劑量組與依那普利組比較無明顯差異(p0.05)。青蒿琥酯能夠顯著降低腎組織MCP-1、TNF-α、TLR4的含量,其各劑量組與模型組比較,差異有統(tǒng)計學(xué)意義(P0.05)；模型組大鼠腎組織見腎小球肥大,系膜區(qū)重度增厚,腎間質(zhì)有炎性細(xì)胞浸潤,各治療組上述變化較模型組有所減輕。結(jié)論：青蒿琥酯對2型糖尿病腎病具有一定的保護(hù)作用,其機制可能部分是通過減輕蛋白尿,減少血肌酐及尿素氮；在蛋白水平上抑制腎組織TLR4的表達(dá)；減少炎性因子MCP-1、TNF-α的分泌,抑制腎臟炎癥反應(yīng),調(diào)節(jié)腎功能,緩解腎臟的病理損害,從而延緩腎臟病變的發(fā)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- 偽 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- 偽 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- 偽, inhibiting renal inflammation, regulating renal function, alleviating the pathological damage of kidney, thus delaying the development of renal disease.
【學(xué)位授予單位】：桂林醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R587.2

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