發(fā)布時間：2019-01-30 18:38

【摘要】：目的:觀察葛根素聯(lián)用格列齊特對2型糖尿病模型大鼠腎臟纖維化的影響，并通過觀察腎臟組織中Ang II含量及MCP-1、TGF-β1表達(dá)的變化，初步探究其作用機(jī)制。 方法:Wistar大鼠64只，隨機(jī)選擇8只為正常對照組，余下大鼠高糖高脂飼養(yǎng)后，采用小劑量腹腔注射35mg·kg-1鏈脲佐菌素(STZ)誘導(dǎo)糖尿病大鼠模型。將造模成功的大鼠隨機(jī)分成6組：模型組（生理鹽水）、格列齊特組(10mg·kg-1·d-1)、葛根素低、中、高劑量組(40、80、160mg·kg-1·d-1)、葛根素聯(lián)用格列齊特組(40mg·kg-1·d-1+5mg·kg-1·d-1)，連續(xù)給藥6周。大鼠麻醉后，腹主動脈取血，檢測有關(guān)指標(biāo)；取腎臟，并稱重，計(jì)算腎臟重量指數(shù)。HE染色觀察大鼠腎臟病理學(xué)改變，Masson染色觀察大鼠腎臟膠原纖維變化。用全自動生化儀測定大鼠血清肌酐(Scr)和尿素氮(BUN)水平；放免法測腎臟組織中Ang II含量；Q-RT-PCR檢測大鼠腎臟組織MCP-1、TGF-β1mRNA的表達(dá)；Western blot檢測腎組織MCP-1、TGF-β1蛋白的表達(dá)。 結(jié)果:①與正常組比較，模型組大鼠體重降低顯著(P＜0.01)；與模型組相比，各治療組大鼠體重降低程度減弱，尤其葛根素聯(lián)用格列齊特組更為顯著（P＜0.01）。②與正常組相比，模型組大鼠血糖、血肌酐、尿素氮水平顯著升高(P＜0.01)；與模型組相比，各治療組大鼠血糖、血肌酐、尿素氮明顯降低，葛根素聯(lián)用格列齊特作用更為明顯(P＜0.01)。③與正常組相比，模型組大鼠腎組織AngⅡ含量、TGF-β1與MCP-1mRNA和蛋白表達(dá)明顯升高；與模型組相比，各劑量組能不同程度降低腎組織AngⅡ含量(P＜0.01或P＜0.05)；除葛根素低劑量組外，其他給藥組均能降低腎臟TGF-β1與MCP-1mRNA和蛋白表達(dá)，其中，聯(lián)合用藥效果最明顯(P＜0.01)。④與正常組比較，模型組大鼠腎小球增大，腎小囊變窄，系膜基質(zhì)增多，腎小管結(jié)構(gòu)混亂；與模型組相比，各治療組大鼠腎臟病理損傷得到不同程度的改善，腎臟膠原沉積顯著改善，其中聯(lián)用組效果最好(P＜0.01)。 結(jié)論:葛根素聯(lián)用格列齊特能顯著改善糖尿病大鼠腎臟纖維化及膠原沉積，，其機(jī)制與兩藥合用降低糖尿病大鼠的血糖，降低腎臟AngⅡ含量，抑制腎臟TGF-β1與MCP-1mRNA及蛋白的表達(dá)有關(guān)。
[Abstract]:Aim: to observe the effect of puerarin combined with gliclazide on renal fibrosis in rats with type 2 diabetes mellitus, and to explore its mechanism by observing the content of Ang II and the expression of MCP-1,TGF- 尾 1 in renal tissue. Methods: Sixty-four Wistar rats were randomly selected as normal control group. The diabetic rats were induced by intraperitoneal injection of 35mg kg-1 streptozotocin (STZ) with low dose of 35mg kg-1 streptozotocin (STZ). The successful rats were randomly divided into 6 groups: model group (normal saline), gliclazide group (10mg kg-1 d-1), low, medium and high dose puerarin group (40,80160 mg kg-1 d-1). Puerarin combined with gliclazide group (40mg kg-1 d-1 5mg kg-1 d-1) was administered continuously for 6 weeks. After anesthesia, blood was taken from abdominal aorta, kidney was taken and weighed, kidney weight index was calculated. Pathological changes of rat kidney were observed by HE staining and collagen fibers were observed by Masson staining. The levels of serum creatinine (Scr) and urea nitrogen (BUN) were measured by automatic biochemical instrument, the content of Ang II in renal tissue was measured by radioimmunoassay, the expression of MCP-1,TGF- 尾 1mRNA in renal tissue was detected by Q-RT-PCR. The expression of MCP-1,TGF- 尾 1 protein in renal tissue was detected by Western blot. Results: 1 compared with the normal group, the weight of the model group decreased significantly (P < 0.01); Compared with the model group, the weight loss was decreased in each treatment group, especially in the puerarin combined with gliclazide group (P < 0.01). 2 compared with the normal group, the blood glucose and creatinine in the model group were significantly lower than those in the control group. Urea nitrogen level increased significantly (P < 0.01). Compared with the model group, blood glucose, serum creatinine and urea nitrogen were significantly decreased in each treatment group, and the effects of puerarin combined with gliclazide were more obvious (P < 0. 01). 3 compared with the normal group, the content of Ang 鈪

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