本文選題：鉤藤堿　切入點(diǎn)：自發(fā)性高血壓大鼠　出處：《皖南醫(yī)學(xué)院》2016年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:觀察鉤藤堿對自發(fā)性高血壓大鼠腎臟纖維化的影響,并探討其機(jī)制。方法:取雄性自發(fā)性高血壓大鼠32只,隨機(jī)分為鉤藤堿高劑量組、鉤藤堿低劑量組、卡托普利陽性對照組、模型組,每組8只;另取WKY大鼠8只作為正常對照組。適應(yīng)性的喂養(yǎng)后,各治療組分別灌胃給予鉤藤堿(10、2.5mg·kg-1·d-1)、卡托普利(17.5 mg·kg-1·d-1),正常對照組和模型組給予蒸餾水(5 ml·kg-1·d-1),共10周。采用尾袖法每2周測定大鼠血壓,末次給藥后,稱量大鼠體重,處死大鼠,鈍性分離腎臟,測量左右腎濕重,計算腎臟重量系數(shù);采用肌氨酸氧化酶法測定血肌酐(Scr),脲酶法測定尿素氮含量(BUN);HE染色觀察腎臟病理組織學(xué)變化,MASSON染色觀察腎臟膠原纖維變化;堿水解法測定腎組織羥脯氨酸(HYP)含量;經(jīng)典的Griess Reagent法測定腎組織一氧化氮(NO)含量;WST-8法測定腎組織超氧化物歧化酶(SOD)含量;比色法測定腎組織丙二醛(MDA)含量;ELISA法檢測血清腫瘤壞死因子α(TNF-α)含量;免疫組化法檢測腎組織轉(zhuǎn)化生長因子-β_1陽性細(xì)胞表達(dá);免疫印跡法檢測腎組織轉(zhuǎn)化生長因子-β_1、Smad3、Smad7、MMP-9、TIMP-1、iNOS蛋白表達(dá)水平。結(jié)果:(1)與WKY組相比,SHR模型組大鼠SBP明顯升高(P0.01);給藥后,鉤藤堿各劑量組的SBP較模型組均有不同程度的降低(P0.01)。(2)與WKY組相比,SHR模型組大鼠腎臟重量指數(shù)明顯升高(P0.01);鉤藤堿高、低劑量組腎臟重量指數(shù)與模型組無明顯差異(P0.05)。(3)與WKY組相比,SHR組大鼠血清Scr、BUN含量明顯升高(P0.01),鉤藤堿高、低劑量組較模型組的血清Scr、BUN含量顯著降低(P0.05或P0.01)。(4)HE染色和Masson染色顯示,SHR組大鼠腎小球基底膜增厚、腎小管萎縮、腎間質(zhì)纖維化伴炎性細(xì)胞浸潤,膠原沉積嚴(yán)重增多,而鉤藤堿各劑量組對上述病理變化均有不同程度的改善。(5)與WKY組相比,SHR組大鼠腎組織HYP、MDA、NO和血清中TNF-α含量顯著升高(P0.01),腎組織SOD含量顯著降低(P0.01);給藥10周后,鉤藤堿各劑量組大鼠腎組織HYP、MDA、NO和血清中TNF-α含量有所降低,腎組織SOD含量顯著升高(P0.05或P0.01);(6)與WKY組相比,SHR組大鼠腎組織TGF-β_1、Smad3、iNOS、MMP-9、TIMP-1蛋白表達(dá)顯著增高,Smad7蛋白表達(dá)降低(P0.01);給藥10周后,鉤藤堿各劑量組能不同程度的降低TGF-β_1、Smad3、iNOS、MMP-9、TIMP-1蛋白表達(dá),升高Smad7蛋白表達(dá)(P0.05或P0.01)。結(jié)論:鉤藤堿能夠降低自發(fā)性高血壓大鼠血壓、改善腎臟纖維化,其機(jī)制可能與調(diào)控TGF-β_1及其下游信號通路、恢復(fù)MMP-9/TIMP-1的平衡、抑制氧化應(yīng)激、降低炎性因子TNF-α含量有關(guān)。
[Abstract]:Objective: to observe the effect of leptinine on renal fibrosis in spontaneously hypertensive rats and to explore its mechanism. Methods: Thirty-two male spontaneously hypertensive rats were randomly divided into high dose group and low dose group. Captopril positive control group, model group, 8 rats in each group, and 8 WKY rats as normal control group. Each treatment group was given Leptacine 102.5 mg kg-1 d -1, captopril 17.5 mg kg-1 d -1, and normal control group and model group were given 5 ml kg-1 d -1 of distilled water for 10 weeks. Blood pressure was measured by tail sleeve method every 2 weeks. After the last administration, the rats were weighed and killed. The kidney was separated obtuse, the wet weight of left and right kidneys was measured, the coefficient of kidney weight was calculated, the serum creatinine was measured by creatine oxidase method, the content of urea nitrogen was determined by urease method, the pathological changes of kidney were observed by HE staining and the changes of collagen fibers in kidney were observed by MASson staining. The content of hydroxyproline (Hyp) in renal tissue was determined by alkaline hydrolysis, the content of nitric oxide (no) in renal tissue by classical Griess Reagent method and the content of superoxide dismutase (SOD) in renal tissue by WST-8 method. The content of malondialdehyde (MDA) in renal tissue was determined by colorimetric method, serum tumor necrosis factor 偽 (TNF- 偽) was detected by Elisa, the expression of transforming growth factor 尾 1 (TGF 尾 1) positive cells in renal tissue was detected by immunohistochemical method. The expression of TGF- 尾 1, Smad3, MMP-9, TIMP-1and iNOS in renal tissue was detected by Western blotting. Results compared with WKY group, the expression of SBP in SHR model group was significantly higher than that in SHR model group (P 0.01). Compared with the WKY group, the renal weight index of the rats in the WKY group was significantly higher than that in the WKY group, and the level of leptinine was higher than that of the model group, and the level of leptinine was higher than that in the WKY group, and the renal weight index of the rats in the WKY group was significantly higher than that in the WKY group. There was no significant difference in renal weight index between the low dose group and the model group (P 0.05. 0. 3) compared with the WKY group, the serum Scrn bun content in the SHR group was significantly higher than that in the WKY group, and the level of leptinine was higher in the low dose group than that in the model group. Compared with the model group, the serum levels of Scrnbun in the low dose group were significantly lower than those in the model group. The results of P0.01).(4)HE staining and Masson staining showed that glomerular basement membrane thickened, tubule atrophy, renal interstitial fibrosis accompanied by inflammatory cell infiltration and collagen deposition were significantly increased in SHR group. Compared with the WKY group, the contents of no and TNF- 偽 in the renal tissue and serum TNF- 偽 in the WKY group were significantly higher than those in the control group, and the content of SOD in the renal tissue was significantly decreased after 10 weeks of administration, while the content of TNF- 偽 in the serum of the rats in the WKY group was significantly higher than that in the control group, while the content of SOD in the renal tissue decreased significantly after 10 weeks of administration. Compared with WKY group, the expression of TGF- 尾 1 Smad3NOSMMP-9 TIMP-1 protein decreased significantly in renal tissue of rats with different doses of leptinine, and the content of TNF- 偽 in renal tissue increased significantly (P 0.05 or P0.01) compared with WKY group, the expression of Smad7 protein decreased 10 weeks after administration of Leptacine, the expression of TGF- 尾 1, Smad3iNOSMMP-9, TIMP-1 protein in renal tissue of rats was significantly decreased, and the expression of TGF- 尾 1, Smad3iNOSMMP-9, TIMP-1 protein decreased significantly in renal tissue compared with WKY group. The expression of TGF- 尾 1 Smad3iNOSU MMP-9 and TIMP-1 was decreased in different dosage groups, and the expression of Smad7 protein was increased (P0.05 or P0.01). Conclusion: Leptosine can reduce blood pressure and improve renal fibrosis in spontaneously hypertensive rats. The mechanism may be related to regulating TGF- 尾-1 and its downstream signaling pathway, restoring the balance of MMP-9/TIMP-1, inhibiting oxidative stress and decreasing the content of inflammatory factor TNF- 偽.
【學(xué)位授予單位】：皖南醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R259

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