發(fā)布時(shí)間：2018-04-01 12:26

  本文選題：Ang1-7　切入點(diǎn)：糖尿病　出處：《天津醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:1.研究不同糖代謝狀態(tài)人群的血管緊張素1-7(Ang 1-7)、血管緊張素轉(zhuǎn)換酶(ACE)2水平,探討其在糖尿病及其并發(fā)癥中的作用。2.制備糖尿病腎臟模型,觀察糖尿病大鼠腎臟病變和評(píng)價(jià)Ang 1-7對(duì)糖尿病大鼠腎臟內(nèi)質(zhì)網(wǎng)應(yīng)激和凋亡的影響。方法:選取2014年12月于天津市海濱人民醫(yī)院95名體檢人員為研究對(duì)象,所有受試者均進(jìn)行口服葡萄糖耐量試驗(yàn),參照《中國2型糖尿病防治指南2010》2型糖尿病診斷標(biāo)準(zhǔn):空腹血糖≥7.0mmol/L,餐后血糖≥11.1mmol/L。血糖異�；颊甙ǹ崭寡鞘軗p(空腹血糖介于6.1~7.0 mmol/L)和餐后血糖調(diào)節(jié)受損(餐后2 h血糖介于7.8~11.1 mmol/L)的患者。根據(jù)血糖水平分為正常組(n=31)、糖耐量異常組(n=32)和糖尿病組(n=32)。檢測(cè)其體重、腰圍、血壓、肝、腎功能、血脂水平、Ang 1-7、血管緊張素轉(zhuǎn)換酶(ACE)2等指標(biāo),評(píng)價(jià)三組患者Ang 1-7水平及與血糖的關(guān)系,進(jìn)一步應(yīng)用多因素非條件Logistic回歸分析影響血糖的危險(xiǎn)因素。選擇20只體重在150-200g之間的健康雄性SD大鼠,隨機(jī)選擇15只給予高脂飼料喂養(yǎng),余下5只給予正常飼料飼養(yǎng)。8周后,給予15只高脂飼養(yǎng)大鼠禁食12小時(shí)(過夜禁食,不禁水),通過腹腔注射鏈脲佐菌素制備糖尿病大鼠模型,5只健康鼠作為對(duì)照組給予注射相當(dāng)體積的檸檬酸緩沖液。結(jié)果,11只成2型糖尿病模型,死亡3只,1只未成模。將糖尿病大鼠隨機(jī)分為兩組,一組給予Ang 1-7(576 ng/d)藥泵干預(yù),為Ang 1-7組,5只。另外一組泵入相當(dāng)體積生理鹽水,為糖尿病組,6只;2周后處死所有大鼠,留取腎臟標(biāo)本。留取血、尿標(biāo)本檢測(cè)血肌酐和24小時(shí)尿蛋白。Western印跡和實(shí)時(shí)熒光定量PCR檢測(cè)分子伴侶葡萄糖調(diào)節(jié)蛋白78(GRP78),增強(qiáng)子結(jié)合蛋白同源蛋白(CHOP)和轉(zhuǎn)錄活性因子4(ATF4)水平。Western印跡和免疫組化檢測(cè)大鼠腎組織凋亡情況。結(jié)果:不同血糖水平人群研究結(jié)果顯示,糖耐量異常組和糖尿病組甘油三酯、ACE2、Ang 1-7水平與對(duì)照組相比明顯升高;糖尿病組較對(duì)照組組明顯升高(p0.017),(TG:3.4±0.9 v.s 1.5±0.8,ACE2:28.6±4.7 v.s 21.8±4.2,Ang 1-7:14.4±4.2 v.s 11.0±3.5);進(jìn)一步多因素非條件Logistic回歸分析顯示,ACE2和Ang 1-7是空腹血糖的獨(dú)立危險(xiǎn)因素。Western印跡結(jié)果顯示,糖尿病組大鼠腎臟組織的內(nèi)質(zhì)網(wǎng)應(yīng)激標(biāo)志蛋白(GRP78、ATF4和CHOP)水平明顯升高,與正常組相比,其差異有統(tǒng)計(jì)學(xué)意義(p0.05);與糖尿病組相比,Ang 1-7組網(wǎng)應(yīng)激標(biāo)志蛋白水平明顯下降,其差異有統(tǒng)計(jì)學(xué)意義(p0.05)。Western印跡和免疫組化顯示Ang 1-7組腎組織caspase 3的表達(dá)較糖尿病組明顯降低。結(jié)論初診糖尿病患者Ang 1-7水平保護(hù)性升高,Ang 1-7可抑制糖尿病大鼠腎臟內(nèi)質(zhì)網(wǎng)應(yīng)激和凋亡。
[Abstract]:Objective: To study 1. patients with different glucose tolerance status of angiotensin 1-7 (Ang 1-7), angiotensin converting enzyme (ACE) level of 2, to explore its role in diabetes and its complications in the preparation of.2. diabetic nephropathy model, to observe the effect of renal lesion in diabetic rats and evaluate Ang 1-7 on diabetic rat kidney endoplasmic reticulum stress and apoptosis. Methods: from December 2014 to the seaside of Tianjin City People's Hospital of 95 medical staff as the object of study, all subjects underwent an oral glucose tolerance test, diagnostic criteria of diabetes with type 2 diabetes prevention guide "China type 2010>2: fasting blood glucose than 7.0mmol/L, postprandial 11.1mmol/L. blood glucose in patients with abnormal blood glucose greater than including impaired fasting glucose (fasting glucose between 6.1~7.0 and mmol/L) impaired postprandial glucose regulation (2 h postprandial blood glucose between 7.8~11.1 mmol/L) patients. According to the blood sugar level in normal group (n=31), Abnormal glucose tolerance group (n=32) and diabetes group (n=32). The detection of body weight, waist circumference, blood pressure, liver, renal function, blood lipid level, Ang 1-7, angiotensin-converting enzyme 2 (ACE) and other indicators, evaluation of three groups of patients with Ang 1-7 level and the relationship with blood glucose, further application of multivariate non conditional Logistic regression analysis of risk factors affecting blood glucose. Healthy male SD rats of 20 body weight between 150-200g, randomly selected 15 rats were given high fat diet, the remaining 5 were given.8 weeks after feeding normal diet, given only 15 in high fat fed rats were fasted for 12 hours (overnight fasting, but not water). The model of diabetes was induced by intraperitoneal injection of streptozotocin, 5 healthy rats as citric acid buffer control group was injected with the equal volume. As a result, 11 type 2 diabetes model, 3 rats died, 1 is not the norm. The diabetic rats were randomly divided into two groups, one Ang group received 1-7 (5 76 ng/d) drug pump intervention, Ang 1-7 group, 5. Another group of equal volume of saline infusion, diabetes group, 6; 2 weeks later, all rats were sacrificed. The kidneys were performed. Blood glucose detection, detection of molecular chaperones of serum creatinine and urine samples of 24 hours urinary protein.Western Western blotting and real-time fluorescent quantitative PCR regulated protein 78 (GRP78), enhancer binding protein homologous protein (CHOP) and transcription factor 4 (ATF4) level of.Western blot and immunohistochemical detection of apoptosis in rat renal tissue. Results: the results showed that people with different blood glucose levels, abnormal glucose tolerance group and diabetes group triglyceride. ACE2, Ang 1-7 levels compared with the control group increased significantly; the diabetic group was significantly increased compared with the control group (p0.017), (TG:3.4 + 0.9 v.s 1.5 + 0.8, ACE2:28.6 + 4.7 v.s 21.8 + 4.2 Ang 1-7:14.4 + 4.2 v.s 11 + 3.5); multivariate non conditional Logistic regression Analysis showed that ACE2 and Ang are 1-7 independent risk factors for fasting blood glucose.Western blot showed that the endoplasmic reticulum stress protein markers in kidney of diabetic rats (GRP78, ATF4 and CHOP) levels were significantly increased, compared with the normal group, the difference was statistically significant (P0.05); compared with the diabetic group, Ang 1-7 network stress marker protein levels were significantly decreased, the difference was statistically significant (P0.05).Western blotting and immunohistochemistry showed that the expression of Ang in renal tissue of 1-7 groups of caspase 3 were significantly lower than those of diabetes mellitus group. Conclusion the Ang patients with newly diagnosed 1-7 diabetes increased the level of protection, Ang 1-7 can inhibit the kidney of diabetic rats on endoplasmic reticulum stress and apoptosis.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R587.2;R692.9

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