本文選題：雌激素 + 大腦中動脈阻塞　； 參考：《南京醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的研究外源性雌激素對去勢雌性大鼠大腦中動脈阻塞(MCAO)模型經(jīng)典Wnt信號通路的影響,探討雌激素在局灶性腦缺血中發(fā)揮神經(jīng)保護(hù)作用的機(jī)制。方法選取SPF級3個(gè)月齡Wistar雌性大鼠60只,采用去勢雌性大鼠腦缺血模型,隨機(jī)分為3組,假手術(shù)組、模型組、雌激素組([17β-雌二醇,皮下注射,300μg/kg·d],每組20只。比較3組大鼠MCAO手術(shù)后24h的死亡率、神經(jīng)功能評分、體質(zhì)量和血清E2水平,2,3,5-三苯基四唑氮紅(TTC)染色法評估腦梗死體積,免疫組織化學(xué)、蛋白質(zhì)印跡法測定左側(cè)大腦皮質(zhì)區(qū)Dickkopf相關(guān)蛋白-1(Dkk-1蛋白)、大腦皮質(zhì)結(jié)腸腺瘤樣息肉病(APC)蛋白、β-連環(huán)蛋白和存活素(Survivin)蛋白的表達(dá)。結(jié)果MCAO手術(shù)后24 h時(shí),假手術(shù)組、模型組、雌激素組大鼠死亡率分別為0、40%(8/20)和20%(4/20),雌激素組神經(jīng)功能評分高于模型組(P0.05),模型組和雌激素組死亡率差異無統(tǒng)計(jì)學(xué)意義(χ~2=1.905,P=0.168)。雌激素組大腦梗死體積([255.43±51.43]mm~3)比模型組([490.75±93.38]mm3)小,2組差異有統(tǒng)計(jì)學(xué)意義(t=5.565P=0.001)。補(bǔ)充外源性雌激素6周再行MCAO手術(shù)后24小時(shí)時(shí),大鼠血清E2水平分別假手術(shù)組(31.36±1.89)pg/mL,模型組(18.23±1.08)pg/mL,雌激素組(35.07±1.46)pg/mL,3組間差異有統(tǒng)計(jì)學(xué)意義(F=253.615,P=0.000);三組大鼠體質(zhì)量分別為假手術(shù)組(207.5±8.657)g,模型組(231.429±16.959)g,雌激素組(197.7±10.382)g,3組間差異有統(tǒng)計(jì)學(xué)意義(F=17.053,P0.001)。免疫組織化學(xué)結(jié)果提示模型組Dkk-1蛋白表達(dá)水平高于其他2組,差異有統(tǒng)計(jì)學(xué)意義(P均0.05);模型組APC蛋白表達(dá)水平高于其他2組,差異有統(tǒng)計(jì)學(xué)意義(P0.05);雌激素組β-連環(huán)蛋白水平高于模型組(P0.05),與假手術(shù)組比較差異無統(tǒng)計(jì)學(xué)意義(P0.05);雌激素組Survivin蛋白表達(dá)高于模型組差異均有統(tǒng)計(jì)學(xué)意義(P均0.05)。蛋白質(zhì)印跡法結(jié)果顯示MCAO手術(shù)后24小時(shí)時(shí),雌激素組DKK-1蛋白表達(dá)低于模型組差異均有統(tǒng)計(jì)學(xué)意義(P0.05);雌激素組APC蛋白表達(dá)低于模型組;β-連環(huán)蛋白的表達(dá)高于模型組,差異均有統(tǒng)計(jì)學(xué)意義(P均0.05);雌激素組Survivin蛋白表達(dá)高于模型組差異均有統(tǒng)計(jì)學(xué)意義(P均0.05)。結(jié)論補(bǔ)充外源性雌激素可以通過下調(diào)皮質(zhì)區(qū)APC蛋白表達(dá),激活經(jīng)典Wnt信號通路,進(jìn)而發(fā)揮在去勢雌性大鼠局灶性腦缺血損傷中的神經(jīng)保護(hù)作用,為絕經(jīng)激素治療降低圍絕經(jīng)期婦女缺血性腦損傷的臨床應(yīng)用提供參考依據(jù)。
[Abstract]:Objective to investigate the effects of exogenous estrogen on the classical Wnt signaling pathway in ovariectomized female rats with middle cerebral artery occlusion (MCAO), and to explore the mechanism of neuroprotective effect of estrogen in focal cerebral ischemia.Methods 60 Wistar female rats of SPF grade 3 months old were randomly divided into 3 groups: sham operation group, model group, estrogen group (17 尾 -estradiol, subcutaneously injected with 300 渭 g/kg d), each group (20 rats).The mortality, neurological function score, body weight and serum E2 level of the three groups were compared 24 hours after MCAO operation to evaluate the volume of cerebral infarction and immunohistochemistry.The expression of Dickkopf associated protein -1 Dkk-1 in left cerebral cortex, adenomatoid polyposis adenomatous polyposis of cerebral cortex, 尾 -catenin and survivin were detected by Western blot.Results at 24 hours after MCAO operation, the mortality of rats in sham operation group, model group and estrogen group were 0 40 / 20 and 20 / 20 respectively. The neurological function score of estrogen group was higher than that of model group (P 0.05). There was no significant difference in mortality between model group and estrogen group (蠂 ~ (21) 1.905 P 0.168).The cerebral infarction volume in estrogen group ([255.43 鹵51.43] mm ~ (-3)) was significantly higher than that in model group ([490.75 鹵93.38] mm ~ (3)).After 6 weeks of supplementation of exogenous estrogen, 24 hours after MCAO operation,The results of immunohistochemistry showed that the expression level of Dkk-1 protein in model group was higher than that in other two groups, the difference was statistically significant (P < 0.05), and the expression level of APC protein in model group was higher than that in other two groups.The level of 尾 -catenin in estrogen group was higher than that in model group (P 0.05), but there was no significant difference between estrogen group and sham operation group (P 0.05), and the expression of Survivin protein in estrogen group was higher than that in model group (P < 0.05).Western blotting showed that the expression of DKK-1 protein in estrogen group was significantly lower than that in model group at 24 hours after MCAO operation, the expression of APC protein in estrogen group was lower than that in model group, and the expression of 尾 -catenin in estrogen group was higher than that in model group.The expression of Survivin protein in estrogen group was higher than that in model group (P < 0.05).Conclusion supplementation of exogenous estrogen can activate the classical Wnt signaling pathway by down-regulating the expression of APC protein in the cortical area and thus play a neuroprotective role in focal cerebral ischemia injury in ovariectomized female rats.To provide reference for the clinical application of menopausal hormone therapy to reduce ischemic brain injury in perimenopausal women.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R-332;R711.75

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