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內(nèi)質(zhì)網(wǎng)應(yīng)激與凋亡在糖尿病周圍神經(jīng)病變中的表達(dá)變化

發(fā)布時(shí)間:2019-01-07 11:45
【摘要】:目的通過構(gòu)建糖尿病周圍神經(jīng)病變(DPN)大鼠模型,觀察DPN大鼠坐骨神經(jīng)中內(nèi)質(zhì)網(wǎng)應(yīng)激與凋亡相關(guān)蛋白表達(dá)變化,探討內(nèi)質(zhì)網(wǎng)應(yīng)激在DPN中的可能作用機(jī)制。方法取36只8周齡雄性Wistar大鼠,適應(yīng)性飼養(yǎng)1周后,選取其中12只作為正常對照組(CON組),其余24只通過高脂飲食結(jié)合腹腔注射鏈脲佐菌素(STZ)方法,將大鼠分別構(gòu)建成糖尿病組(DM組,12只)、DPN組(12只)模型。造模成功后檢測3組大鼠血糖與坐骨神經(jīng)傳導(dǎo)速度,并取大鼠坐骨神經(jīng),采用Western blotting方法檢測內(nèi)質(zhì)網(wǎng)應(yīng)激蛋白CHOP、PERK與凋亡相關(guān)蛋白Bax、Caspase-12、Bcl-2表達(dá)水平。結(jié)果與CON組比較,DM組血糖水平明顯升高(P0.001),運(yùn)動(dòng)神經(jīng)傳導(dǎo)速度明顯減慢(P0.001);內(nèi)質(zhì)網(wǎng)應(yīng)激蛋白CHOP、PERK表達(dá)水平增加(P=0.003,P0.001);促凋亡蛋白Bax、Caspase-12表達(dá)增加(P0.001,P0.001),抗凋亡蛋白Bcl-2表達(dá)降低(P0.001)。與DM組比較,DPN組大鼠坐骨神經(jīng)內(nèi)質(zhì)網(wǎng)應(yīng)激蛋白CHOP、PERK表達(dá)水平增加(P0.001,P=0.01),Bax、Caspase-12表達(dá)增加(P0.001,P=0.002),Bcl-2表達(dá)水平降低(P0.001)。結(jié)論 DPN大鼠模型坐骨神經(jīng)存在明顯的內(nèi)質(zhì)網(wǎng)應(yīng)激反應(yīng)增加、凋亡上調(diào),內(nèi)質(zhì)網(wǎng)應(yīng)激參與了DPN的發(fā)生過程。
[Abstract]:Objective to observe the changes of endoplasmic reticulum stress and apoptosis-related protein expression in sciatic nerve of (DPN) rats with diabetic peripheral neuropathy and to explore the possible mechanism of endoplasmic reticulum stress in DPN. Methods Thirty-six 8-week-old male Wistar rats were fed adaptively for one week, 12 of them were used as normal control group (CON group), the other 24 rats were treated by high-fat diet and intraperitoneal injection of streptozotocin (STZ). The rats were divided into diabetic group (DM group) and), DPN group (12 rats). The blood glucose and the conduction velocity of sciatic nerve were measured after the model was established. The expression of endoplasmic reticulum stress protein (CHOP,PERK) and apoptosis-related protein (Bax,Caspase-12,Bcl-2) were detected by Western blotting method. Results compared with the CON group, the blood glucose level in the DM group was significantly increased (P0.001), the motor nerve conduction velocity was significantly decreased (P0.001), the expression of endoplasmic reticulum stress protein CHOP,PERK was increased (P0. 003 + P0. 001). The expression of pro-apoptotic protein Bax,Caspase-12 increased (P0.001 + P0.001), and the expression of anti-apoptotic protein Bcl-2 decreased (P0.001). Compared with DM group, the expression of ER stress protein CHOP,PERK, Bax,Caspase-12 and Bcl-2 in DPN group were increased (P0.001P0. 01) and decreased (P0. 001). Conclusion there are obvious endoplasmic reticulum stress responses and up-regulation of apoptosis in sciatic nerve of DPN rats. Endoplasmic reticulum stress is involved in the process of DPN.
【作者單位】: 山東大學(xué)第二醫(yī)院內(nèi)分泌科;
【基金】:國家自然科學(xué)基金(81670753) 中華醫(yī)學(xué)會(huì)臨床醫(yī)學(xué)科研專項(xiàng)資金(13020230408) 山東大學(xué)第二醫(yī)院種子基金(S2014010004)
【分類號(hào)】:R587.2

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