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目的:探讨牛磺熊去氧胆酸(TUDCA)抗大鼠肝脏缺血再灌注(HIRI)损伤的作用及机制。方法:将20只雄性SD大鼠随机均分为假手术组、TUDCA组、HIRI组、TUDCA+HIRI组,分别行假手术、TUDCA+假手术、HIRI造模,TUDCA+HIRI造模;TUDCA(250 mg/kg)于术前1 h灌胃给予,HIRI造模采用Pringle法(缺血60 min,再灌注12 h)。再灌注12 h后处死各组大鼠取材,观察肝组织病理学改变,检测血清谷丙转氨酶(ALT)水平,TUNEL法检测肝细胞凋亡,Western blot技术检测肝组织内质网应激分子糖调节蛋白78(GRP78)、p-真核细胞翻译起始因子2α(p-e IF2α)和C-EBP同源蛋白(CHOP)的表达。结果:除假手术组与TUDCA组外,HIRI组与TUDCA+HIRI组大鼠肝组织均出现明显肝损伤病理改变,但TUDCA+HIRI组的损伤程度明显轻于HIRI组。与假手术组比较,HIRI组与TUDCA+HIRI组大鼠血清ALT水平明显升高,肝细胞凋亡和内质网应激分子GRP78、p-e IF2a和CHOP蛋白水平均明显升高(均P<0.05),但TUDCA+HIRI组各项指标升高幅度均明显低于HIRI组(均P<0.05);TUDCA组各项指标未见改变(均P>0.05)。结论:TUDCA有抗大鼠肝HIRI的作用,其机制可能与抑制内质网应激反应有关。
Objective: To investigate the effect and mechanism of TUDCA on liver ischemia-reperfusion (HIRI) injury in rats. Methods: Twenty male Sprague-Dawley rats were randomly divided into sham operation group, TUDCA group, HIRI group and TUDCA + HIRI group. Sham operation, TUDCA + sham operation, HIRI modeling and TUDCA + mg / kg) were given intragastrically at 1 h before surgery. Pringle method was used to establish HIRI model (ischemia 60 min, reperfusion 12 h). After reperfusion for 12 h, the rats in each group were sacrificed and pathological changes of liver tissues were observed. Serum alanine aminotransferase (ALT) level was measured. TUNEL assay was used to detect hepatocyte apoptosis. Western blot was used to detect the endoplasmic reticulum stress molecular sugar Regulatory protein 78 (GRP78), p-eukaryotic translation initiation factor 2 alpha (pe IF2 alpha), and C-EBP cognate protein (CHOP). Results: The pathological changes of hepatic tissue in HIRI group and TUDCA + HIRI group were obvious except for the sham operation group and TUDCA group, but the damage degree in TUDCA + HIRI group was lighter than that in HIRI group. Compared with the sham-operation group, serum ALT levels in HIRI group and TUDCA + HIRI group were significantly increased, hepatocyte apoptosis and ER stress protein GRP78, pe IF2a and CHOP levels were significantly increased (all P <0.05 ), But the indexes in TUDCA + HIRI group were significantly higher than those in HIRI group (all P <0.05). No significant changes were found in TUDCA group (all P> 0.05). Conclusion: TUDCA has anti-HIRI effect on rat liver, and its mechanism may be related to inhibition of endoplasmic reticulum stress response.