本文選題：替米沙坦　切入點：胰島素抵抗　出處：《天津醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的本實驗以高脂飼料飼養(yǎng)自發(fā)性高血糖大鼠(otsuka long-evans tokushima fatty,OLETF),胰島素抵抗(insulin resistance,IR)實驗動物模型造模成功后,以替米沙坦進(jìn)行藥物干預(yù),旨在:1、研究IR-OLETF大鼠心房肌L型鈣通道α1C亞單位(L-type calcium channelα1C subunit,Cav1.2)的表達(dá)水平;2、研究血管緊張素II受體1型拮抗劑(angiotensin II type 1 receptor blocker,ARB)替米沙坦對IR-OLETF大鼠的心房肌Cav1.2蛋白表達(dá)的影響;3、探討替米沙坦對心房肌Cav1.2蛋白表達(dá)的影響及其改善IR的可能機(jī)制。方法LETO(long-evans tokushima fatty)大鼠(雄性,1月齡,無特定病原體級)共計16只,OLETF大鼠(雄性,1月齡,無特定病原體級)共計32只,,體質(zhì)量范圍在135至185g,所有實驗動物在標(biāo)準(zhǔn)飼料及干凈整潔環(huán)境條件下適應(yīng)性飼養(yǎng)1月。在2月齡時,所有OLETF大鼠以高脂飼料進(jìn)行喂養(yǎng),于7月齡時停止進(jìn)食12小時后于股靜脈處取血,測定所有實驗動物的血清胰島素(fasting insulin,FINS)、空腹血糖(fasting blood glucose,FBG)的數(shù)值,并通過相關(guān)公式分析得出胰島素抵抗指數(shù)(insulin resistance index,HOMS-IR),分析大鼠胰島素抵抗模型是否造模成功。用隨機(jī)數(shù)字表法將32只造模成功的IR-OLETF大鼠分為2組,16只模型組(M)的大鼠繼續(xù)以高脂飼料飼養(yǎng),16只替米沙坦(T)組大鼠以高脂飼料飼養(yǎng)并加用替米沙坦(5mg/kgd)進(jìn)行干預(yù),16只LETO大鼠作為正常對照(NC)組,始終以標(biāo)準(zhǔn)飼料進(jìn)行飼養(yǎng)。按上述方法飼養(yǎng)大鼠5月后,所用大鼠再次停止進(jìn)食12小時后于股靜脈處取血,通過放射免疫法檢測FINS,以葡萄糖酶法檢測FBG,使用全自動生化分析儀檢測甘油三酯(triglyceride,TG)、高密度脂蛋白(high density lipoprotein cholesterol,HDL-C)、總膽固醇(total cholesterol,TC)及低密度脂蛋白(low density lipoprotein cholesterol,LDL-C)。然后使用脊椎脫臼法處死所用大鼠,迅速取出實驗動物內(nèi)臟(心臟、肝臟、腎臟、眼球等)組織保存于凍存管中,置入-80℃冰箱中低溫密閉封存,使用為蛋白質(zhì)印跡法檢測所有實驗動物心房肌組織中Cav1.2蛋白的表達(dá)量。采用SPSS20.0統(tǒng)計軟件將所得結(jié)果進(jìn)行計算分析。結(jié)果1、三組間實驗大鼠的FINS,FBG,HOMA-IR的比較:T組和M組比較,FINS,FBG,HOMA-IR的數(shù)值明顯降低,差異具有統(tǒng)計學(xué)意義;和NC組相比較,M組的FINS,FBG,HOMA-IR的數(shù)值顯著增高,差異具有統(tǒng)計學(xué)意義(P0.05)。2、三組間實驗大鼠血脂代謝水平的比較:T組和M組比較,LDL-C,TG,TC的數(shù)值顯著降低,差異具有統(tǒng)計學(xué)意義(P0.05)。但HDL-C的數(shù)值無明顯改變,差異無統(tǒng)計學(xué)意義(P=0.384);M組LDL-C,TG,TC的數(shù)值明顯高于NC組,HDL-C數(shù)值明顯低于NC組。3、三組間實驗大鼠心房肌組織Cav1.2蛋白表達(dá)含量的比較:T組與M組相比,心房肌組織中Cav1.2蛋白水平明顯升高,M組與NC組相比,心房肌組織中Cav1.2蛋白水平明顯降低,差異有統(tǒng)計學(xué)意義(P0.05)。結(jié)論1、通過高脂飼養(yǎng)并成功建立胰島素抵抗模型的OLETF大鼠血清中FINS,FBG,HOMA-IR,TG、LDL-C和TC數(shù)值顯著升高,HDL-C數(shù)值顯著降低。2、替米沙坦干預(yù)后,IR大鼠血清FBG,FINS,HOMA-IR,TC,TG和LDL-C水平明顯降低,表明替米沙坦可以通過改善IR大鼠的糖脂代謝,改善其胰島素抵抗。3、OLETF大鼠心房肌組織中Cav1.2的表達(dá)水平發(fā)現(xiàn),胰島素抵抗大鼠心房肌組織中Cav1.2蛋白的含量明顯減少,而使用替米沙坦進(jìn)行藥物干預(yù)后其表達(dá)水平回升。
[Abstract]:The purpose of this experiment is fed with the high-fat diet in spontaneous hyperglycemic rats (Otsuka Long-Evans, Tokushima fatty, OLETF), insulin resistance (insulin resistance, IR) experimental animal model successfully, with telmisartan for drug intervention, aimed at: 1, atrial L research IR-OLETF rat calcium channel alpha subunit 1C (L-type calcium channel 1C subunit Cav1.2) alpha, the expression level; 2, study of angiotensin II type 1 receptor antagonist (angiotensin II type 1 receptor blocker, ARB) expression of telmisartan on IR-OLETF rat atrial muscle Cav1.2 protein; 3, to explore the possible mechanism of effect of telmisartan on the expression of Cav1.2 protein and atrial muscle improvement of IR method. LETO (Long-Evans Tokushima fatty) rats (male, 1 month old, specific pathogen free) a total of 16, OLETF rats (male, 1 month old, specific pathogen free), a total of 32, weight range In 135 to 185g, all the experiments in the standard animal feed and clean environment. In January 2 month old adaptive feeding, all OLETF rats were fed with high-fat diet, in 7 month old when to stop eating 12 hours after the blood samples were collected from the femoral vein, serum insulin were measured in all experimental animal (fasting insulin FINS) fasting blood glucose (fasting blood, glucose, FBG) value, and the insulin resistance index by correlation analysis formula (insulin resistance index, HOMS-IR), analysis of rat model of insulin resistance is the successful model. By the method of random number table 32 successful model of IR-OLETF rats were divided into 2 groups, 16 rats group (M) to rats by high fat diet, 16 telmisartan (T) group of rats fed with the high-fat diet combined with telmisartan (5mg/kg? D) intervention, 16 LETO rats as normal control group (NC), always with a standard diet According to the above method for feeding. Rats after May, rats used again to stop eating 12 hours after the blood samples were collected from the femoral vein, detected by FINS radioimmunoassay to detect FBG glucose enzymatic method, using automatic biochemical analyzer to detect triglyceride (triglyceride, TG), high density lipoprotein (high density lipoprotein cholesterol, HDL-C), total cholesterol (total, cholesterol, TC) and low density lipoprotein (low density lipoprotein cholesterol, LDL-C). Then use the spinal dislocation method executed by rats, quickly remove the experimental animal organs (heart, liver, kidney, eye) tissue preserved in freezing tube, using -80 C low temperature refrigerator sealed, used for Western blotting to detect the expression of Cav1.2 protein in all experimental animal atrial tissue in quantity. Using statistical software SPSS20.0 the results were calculated and analyzed. Results of the 1, between the three groups. Experimental rats FINS, FBG, HOMA-IR: T, group M and group FINS, FBG, HOMA-IR were significantly decreased, the difference was statistically significant; and NC group compared with M group, FINS, FBG, HOMA-IR values were significantly higher, the difference was statistically significant (P0.05.2), comparative experiment the lipid metabolism in rats: a comparison between the three groups, T group and M group LDL-C, TG, TC values decreased significantly, the difference was statistically significant (P0.05). But no significant changes in the value of HDL-C, the difference was not statistically significant (P=0.384); group M LDL-C, TG, TC value was significantly higher than NC group HDL-C numerical, significantly lower than NC group.3, between the three groups the expression of Cav1.2 protein in atrial tissue were compared in rats: compared with T group and M group, Cav1.2 protein levels in atrial tissue were significantly higher in M group compared with NC group, Cav1.2 protein levels in atrial tissue were significantly decreased, the difference was statistically significant (P0.05). Conclusion: 1, through High fat diet and successfully established FINS, OLETF in serum of rat model of insulin resistance in FBG, HOMA-IR, TG, LDL-C and TC values were significantly increased, HDL-C value decreased significantly.2 telmisartan intervention, serum FBG, rat IR FINS, HOMA-IR, TC, TG and LDL-C were significantly decreased, that of telmisartan can glycolipid improve the metabolism of IR rats, improve the insulin resistance of.3, the expression level of Cav1.2 in atrial tissue in OLETF rats found that insulin resistance Cav1.2 protein content of atrial tissue in rats was significantly reduced, and the use of drug intervention of telmisartan and its expression level rise.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R589.2

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相關(guān)期刊論文 前1條

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本文編號：1701636