牛磺熊去氧胆酸对大鼠肝脏缺血再灌注损伤的保护作用
| 作者: |
1何宗全,
1章安庆,
1叶显道,
1胡磊,
1朱文俊
1 安徽省铜陵市人民医院 肝胆一科，安徽 铜陵 244000 |
| 通讯: |
何宗全
Email: hezongquan@126.com |
| DOI: | 10.3978/.10.3978/j.issn.1005-6947.2015.07.013 |
| 基金: | 安徽省铜陵市卫生局科研资助项目, 卫科研[2012]10 |
摘要
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-eIF2α）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-eIF2a 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。
关键词：
肝
再灌注损伤
凋亡
内质网应激
Protective effect of tauroursodeoxycholic acid against hepatic ischemia reperfusion injury in rats
CorrespondingAuthor:HE Zongquan Email: hezongquan@126.com
Abstract
Objective: To investigate the protective effect of tauroursodeoxycholic acid (TUDCA) against hepatic ischemia reperfusion injury (HIRI) in rat and the mechanism. Methods: Twenty male SD rats were equally randomized into sham operation group, TUDCA group, HIRI group and TUDCA plus HIRI group, and underwent sham operation, TUDCA treatment plus sham operation, HIRI model induction, and TUDCA treatment plus HIRI model induction, respectively. TUDCA (250 mg/kg) was administered by gavage 1 h before operation, and HIRI rat model was induced by Pringle maneuver (60-min hepatic ischemia followed by 12-h reperfusion). Rats in each group were sacrificed after 12-h reperfusion and the hepatic samples were collected; the pathological changes in liver tissues were observed, serum alanine aminotransferase (ALT) level was measured, apoptosis of hepatic cells was determined by TUNEL staining, and the proteins associated with endoplasmic reticulum (ER) stress which included glucose regulate protein 78(GRP78), p-eukaryotic translation initiation factor-2α (p-eIF2α) and C-EBP response element binding protein (CHOP) were determined by Western blot analysis. Results: Except in sham operation group and TUDCA group, the liver tissues in either HIRI group or TUDCA plus HIRI group presented the evident pathological changes associated with liver injury, but the degree of injury in TUDCA plus HIRI group was milder than that in HIRI group. Compared with sham operation group, the serum ALT levels, hepatic cell apoptosis and the protein expression levels of GRP78, p-eIF2a and CHOP in liver tissues were significantly increased in both HIRI group and TUDCA plus HIRI group (all P<0.05), but the increasing amplitudes of all these parameters in TUDCA plus HIRI group were significantly less than those in HIRI group (all P<0.05); all the parameters in TUDCA showed no significant alteration (all P>0.05). Conclusion: TUDCA has protective effect against HIRI in rats, and the mechanism may probably be associated with its suppression of ER stress response.
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