本文選題：白藜蘆醇　切入點(diǎn)：SIRT1　出處：《重慶醫(yī)科大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

【摘要】：目的檢測炎癥反應(yīng)調(diào)節(jié)因子NF-κB及去乙�；窼IRT1在正常胎盤組織及ICP胎盤組織的蛋白表達(dá)情況;探討�；悄懰�(Taurocholic acid,TCA)誘導(dǎo)胎盤合體滋養(yǎng)細(xì)胞系HTR-8細(xì)胞的炎癥反應(yīng),及白藜蘆醇對HTR-8細(xì)胞炎癥反應(yīng)的抑制作用及機(jī)制。方法收集臨床胎盤標(biāo)本及肝功能指標(biāo)(正常、ICP輕度和ICP重度),免疫組化及免疫印跡法檢測SIRT1以及NF-κB的定位以及蛋白表達(dá)情況。不同濃度TCA處理HTR-8細(xì)胞24小時(shí)(組11:TCA=0μmol/L,組2:TCA=2μmol/L,組3:TCA=20μmol/L,組4:TCA=100μmol/L),免疫熒光及免疫印跡法檢測SIRT1定位,SIRT1、NF-κB和TNF-α蛋白表達(dá)情況。SIRT1激動(dòng)劑白藜蘆醇(resveratrol,Res)處理各組細(xì)胞24小時(shí),SIRT1抑制劑Ex-527與白藜蘆醇同時(shí)處理各組細(xì)胞24小時(shí),免疫印跡法檢測處理后SIRT1、NF-κB及TNF-α蛋白表達(dá)的變化情況。結(jié)果SIRT1與NF-κB主要表達(dá)于胎盤合體滋養(yǎng)細(xì)胞的細(xì)胞質(zhì)和細(xì)胞核。SIRT1蛋白在ICP胎盤組織的表達(dá)低于正常胎盤組織,NF-κB蛋白在ICP胎盤組織的表達(dá)高于正常胎盤組織;SIRT1蛋白在組3和組4中的表達(dá)低于組1和組2中的表達(dá),NF-κB及TNF-α蛋白在組3和組4中的表達(dá)高于組1和組2中的表達(dá)。差異均具有統(tǒng)計(jì)學(xué)意義(P0.05)。使用白藜蘆醇處理組3和組4后,SIRT1蛋白表達(dá)升高,NF-κB及TNF-α蛋白的表達(dá)降低(P0.05);Ex-527加白藜蘆醇同時(shí)處理組3及組4,與單獨(dú)使用白藜蘆醇處理相比,SIRT1蛋白表達(dá)降低,NF-κB及TNF-α蛋白表達(dá)升高,差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論ICP胎盤合體滋養(yǎng)細(xì)胞SIRT1表達(dá)下調(diào),NF-κB及TNF-α表達(dá)上調(diào),其可能的機(jī)制是ICP高濃度膽汁酸干擾胎盤合體滋養(yǎng)細(xì)胞SIRT1-NF-κB通路,誘導(dǎo)炎癥反應(yīng),SIRT1激動(dòng)劑白藜蘆醇可逆轉(zhuǎn)這一過程。
[Abstract]:Objective to detect the protein expression of NF- 魏 B and deacetylase SIRT1 in normal placenta and ICP placenta, and to investigate the inflammatory response induced by Taurocholic acidic acid (Taurocholic acidic acid) in human placental syncytiotrophoblast cell line HTR-8. Methods placental specimens and liver function indexes (mild and severe ICP) were collected, and the localization of SIRT1 and NF- 魏 B were detected by immunohistochemistry and Western blotting. Protein expression: HTR-8 cells were treated with different concentrations of TCA for 24 hours (group 11: TCA 0 渭 mol / L, group 2: TCA 2 渭 mol / L, group 3: TCA 20 渭 mol / L, group 4: TCA 100 渭 mol / L). Immunofluorescence and Western blotting were used to detect the expression of SIRT1 localization of SIRT1 NF- 魏 B and TNF- 偽 protein. Ex-527, an inhibitor of SIRT1, was treated with resveratrol for 24 hours. Results the expression of SIRT1 and NF- 魏 B in cytoplasm and nucleus of placenta syncytiotrophoblast was lower than that of normal placenta tissue in ICP placenta. The expression of TNF- 魏 B and TNF- 偽 protein in ICP placenta tissue was higher than that in normal placental tissue in group 3 and group 4. The expression of NF- 魏 B and TNF- 偽 protein in group 3 and group 2 was higher than that in group 1 and group 2. The expression of sir1 protein increased after resveratrol treatment group 3 and 4. The expression of NF- 魏 B and TNF- 偽 protein decreased in group 3 and group 4 after resveratrol treatment, and compared with resveratrol alone in group 3 and group 4. The expression of SIRT1 protein decreased and the expression of NF- 魏 B and TNF- 偽 protein increased. Conclusion the expression of SIRT1 in placental syncytiotrophoblast of ICP is down-regulated, and the expression of TNF- 魏 B and TNF- 偽 is up-regulated. The possible mechanism is that the high concentration of ICP bile acid interferes with the SIRT1-NF- 魏 B pathway of placental syncytiotrophoblast. Resveratrol, an agonist of SIRT1, can reverse this process.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R714.255

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