本文選題：胰島β細(xì)胞　切入點(diǎn)：凋亡　出處：《廣西醫(yī)科大學(xué)》2015年碩士論文

【摘要】：研究目的： 通過(guò)建立糖尿病前期小鼠胰島p細(xì)胞凋亡模型,研究厄貝沙坦對(duì)胰島p細(xì)胞凋亡及氧化應(yīng)激的影響,明晰其介導(dǎo)細(xì)胞凋亡和氧化應(yīng)激通路中的角色扮演。研究方法： (1)糖尿病前期小鼠胰島p細(xì)胞凋亡模型的建立：選取雄性BABL/C小鼠,分別予60mg/kg、80mg/kg、100mg/kg小劑量STZ腹腔注射,觀察時(shí)點(diǎn)分別為干預(yù)后6h、12h和24h,監(jiān)測(cè)血糖、胰腺HE染色以Tunel檢測(cè)胰島p細(xì)胞凋亡率。 (2)厄貝沙坦+STZ組：300mg/kg厄貝沙坦灌胃一周后予腹腔注射80mg/kg STZ; STZ組：腹腔注射80mg/kg STZ;正常對(duì)照組：無(wú)任何干預(yù)。行HE染色、免疫組織化學(xué)、Tunel檢測(cè),采用real-timePCR檢測(cè)AT1R、Caspase-3、P38MAPK、ROS及NADPH mRNA表達(dá)。研究結(jié)果： (1)糖尿病前期小鼠胰島β細(xì)胞凋亡模型的建立：在所有測(cè)試時(shí)點(diǎn)血糖均在6-11mmol/L范圍內(nèi)波動(dòng),未達(dá)到糖尿病模型范疇。與對(duì)照組相比,實(shí)驗(yàn)組各時(shí)點(diǎn)的胰島p細(xì)胞凋亡率均明顯升高(P0.05)；各實(shí)驗(yàn)組均在12h時(shí)點(diǎn)凋亡率達(dá)到最高峰,并且80mg/kg組與60mg/kg、100mg/kg相比明顯升高(P0.05)。 (2)厄貝沙坦對(duì)糖尿病前期小鼠胰島p細(xì)胞凋亡機(jī)制的研究：與對(duì)照組比較,厄貝沙坦+STZ組及STZ組血糖、凋亡率均明顯升高(P0.000),但血糖水平10mmol/L。與STZ組相比,厄貝沙坦+STZ組胰島p細(xì)胞凋亡率明顯下降(P0.001)。厄貝沙坦+STZ組胰島素的表達(dá)量較STZ組有所上升(P0.001)。在STZ組,胰腺組織中AT1R、Caspase-3 mRNA及氧化應(yīng)激相關(guān)指標(biāo)P38MAPK, ROS和NADPH mRNA表達(dá)增加(P0.05)。經(jīng)過(guò)厄貝沙坦干預(yù)后,各指標(biāo)mRNA的表達(dá)均呈下調(diào)趨勢(shì)(P0.05)。結(jié)論： (1)單次小劑量STZ誘導(dǎo)的小鼠胰島p細(xì)胞凋亡在STZ注射后12h出現(xiàn)凋亡高峰。在本研究中80mg/kg濃度的STZ在12h的胰島p細(xì)胞凋亡率最高,提示建模成功。 (2)經(jīng)過(guò)厄貝沙坦灌胃預(yù)處理后再予注射STZ可以降低胰島p細(xì)胞凋亡率。注射STZ后可以引起小鼠胰島細(xì)胞AT1R表達(dá)升高,引起胰島細(xì)胞凋亡損傷可能與RAS系統(tǒng)激活有關(guān)。STZ可以引起胰島細(xì)胞氧化應(yīng)激水平的升高和細(xì)胞凋亡的增加,而厄貝沙坦早期干預(yù)通過(guò)降低P38MAPK、Caspase-3和ROS、NADPH的表達(dá),有效降低氧化應(yīng)激和細(xì)胞凋亡而達(dá)到保護(hù)胰島細(xì)胞的作用。
[Abstract]:Objective: to study the effects of irbesartan on pancreatic islet p cell apoptosis and oxidative stress by establishing a model of islet p cell apoptosis in prediabetic mice. Methods: to establish a model of pancreatic islet p cell apoptosis in prediabetic mice: male BABL/C mice were injected intraperitoneally with 60 mg / kg 80 mg / kg / kg 100 mg / kg STZ, respectively. The observed time points were 12 h and 24 h after intervention, respectively, and blood glucose was monitored. Pancreatic HE staining was used to detect the apoptosis rate of pancreatic islet p cells by Tunel. (2) Irbesartan STZ group (1: 300 mg / kg irbesartan) was intraperitoneally injected with 80mg/kg STZ one week after gavage; STZ group was intraperitoneally injected with 80mg/kg STZ; normal control group was treated with HE staining without any intervention. Immunohistochemical Tunel assay and real-timePCR were used to detect the expression of AT1RnCaspase-3p38MAPKROS and NADPH mRNA. Results: 1) Establishment of islet 尾 cell apoptosis model in prediabetic mice: blood glucose fluctuated in the range of 6-11mmol/L at all test points. Compared with the control group, the apoptotic rate of pancreatic islet p cells in the experimental group was significantly higher than that in the control group, and the apoptotic rate reached the peak at 12 h in each experimental group. In addition, compared with 60 mg / kg 100 mg / kg 80mg/kg group, the mechanism of irbesartan on apoptosis of islet p cells in prediabetic mice was significantly higher than that in 60 mg / kg / kg 80mg/kg group. Compared with the control group, the blood glucose of irbesartan STZ group and STZ group was significantly higher than that of the control group. The apoptotic rate was significantly increased, but the blood glucose level was 10 mmol / L. Compared with the STZ group, the apoptotic rate of islet p cells in irbesartan STZ group was significantly lower than that in the STZ group. The expression of insulin in irbesartan STZ group was higher than that in STZ group. In STZ group, the expression of insulin in irbesartan STZ group was significantly higher than that in STZ group. The expression of Caspase-3 mRNA and P38 MAPK, ROS and NADPH mRNA in pancreatic tissue increased after irbesartan intervention. The expression of mRNA was down-regulated (P 0.05). Conclusion: the apoptosis of islet p cells induced by a single low dose of STZ reached a peak at 12 h after STZ injection. In this study, the apoptotic rate of islet p cells was the highest at the concentration of 80mg/kg at 12 h. It was suggested that the model was successfully established. (2) injection of STZ after irbesartan intragastric preconditioning could reduce the apoptosis rate of islet p cells and increase the expression of AT1R in islet cells of mice after injection of STZ. The apoptosis injury of islet cells may be related to the activation of RAS system. STZ may induce the increase of oxidative stress and apoptosis of pancreatic islet cells, and the early intervention of irbesartan can reduce the expression of P38 MAPKCaspase-3 and Rosna DPH. The protective effect of islet cells was achieved by reducing oxidative stress and apoptosis.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R587.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 邵加慶;顧萍;杜宏;盧斌;李潔;彭麗;王燕燕;趙明;王堅(jiān);;替米沙坦對(duì)db/db小鼠胰島內(nèi)NADPH氧化酶表達(dá)水平的影響[J];醫(yī)學(xué)研究生學(xué)報(bào);2010年07期

2 鄭倩;劉紅;劉華;曹弟勇;蘭海濤;;果糖二磷酸鈉對(duì)2型糖尿病大鼠胰島內(nèi)質(zhì)網(wǎng)應(yīng)激時(shí)CHOP和JNK表達(dá)及胰島細(xì)胞凋亡的影響[J];中國(guó)病理生理雜志;2012年04期

3 高會(huì)敏;蒙碧輝;韋靜彬;陳洪流;林媛媛;;羅格列酮對(duì)實(shí)驗(yàn)性1型糖尿病大鼠胰島β細(xì)胞凋亡的影響[J];重慶醫(yī)科大學(xué)學(xué)報(bào);2011年11期

相關(guān)博士學(xué)位論文 前2條

1 梁杏歡;體外高糖誘導(dǎo)SD大鼠胰島細(xì)胞凋亡與厄貝沙坦的干預(yù)研究[D];廣西醫(yī)科大學(xué);2008年

2 李新;阻斷腎素血管緊張素系統(tǒng)對(duì)胰島β細(xì)胞功能的效應(yīng)及機(jī)制研究[D];華中科技大學(xué);2009年

，

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