去肝动脉化对阻塞性黄疸大鼠肝脏损伤的初步研究

Preliminary study on hepatic impairment after hepatic artery ligation in rats with obstructive jaundice

目的:研究胆道梗阻不同时段大鼠能否结扎肝动脉及其机制。方法:雄性SD大鼠96只,随机分为对照组(C组)、肝动脉结扎组(HAL组)、胆道梗阻7d+肝动脉结扎组(BDL7+HAL组)及胆道梗阻14d+肝动脉结扎组(BDL14+HAL)。术后1d、3d、7d留取血及肝脏标本测定肝功能、肝组织HIF-1α(hypoxic-inducible factor-1α,缺氧诱导因子-1α)蛋白表达及病理变化。结果:肝动脉结扎后,各组的1周存活率分别为8/8、8/8、5/6、6/7;各组ALT、AST、TBIL水平均升高,术后1d达最高值。HAL组术后7d基本恢复正常;BDL7+HAL及BDL14+HAL组术后7d仍明显高于对照组和肝动脉结扎组(P<0.05)。免疫组化显示HIF-1α阳性细胞主要位于肝中央静脉周围。术后3d,HAL组HIF-1α蛋白较对照组明显增高(7.8±3.2)%vs(2.1±1.4)%;术后1d,BDL14+HAL组HIF-1α蛋白较BDL7+HAL组明显增高(8.1±3.5)%vs(3.5±2.3)%。肝脏组织学检查,各组可见程度不同的肝细胞变性、坏死,炎细胞浸润,小胆管增生和胶原组织增生。结论:胆道梗阻大鼠在解除胆道梗阻后可以耐受肝动脉结扎,但肝功能损害较重,其机制可能与术后侧枝循环的建立诱导HIF-lα表达变化有关。

Objective：To examine the effecls and mechanism in rats undergone hepatic artery ligation at regular intervals. Methods： Ninety-six male Sprague-Dawley rats were randomized into groups of the controls （group C）, hepatic artery ligation （group HAL）, 7 days of biliary ob-struction plus hepatic artery ligation （ group BDL7 ＋ HAL） and 14 days of biliary obstruction along with hepatic artery ligation （group BDLI4 ＋ HAL）. The liver and blood samples were taken at the day of the 1st, 3rd and 7th, respectively, after modeling for determining the liver function and the pathological changes and detecting the expression of bypoxic- inducible faetor-lα（HIF-lα）. Results：The survival rate of 1-week in each group was 8/8 ,8/ 8, 5/ 6 and 6/7, respectively, after hepatic artery ligatiou. The levels of alanine transarninase （ ALT ）, aspartate aminotransferase（AST） and total bilirubin（TBIL） were elevated after hepatic artery ligation, with the peak at dl. The indicators described above returned normally in the group of HAL after 7 days of the intervention, but were much higher at the 7th day in groups of BDL7 ＋ HAL and BDLI4 ＋ HAL as compared with HAL and the controls（ P 〈0.05 ）. Positive HIF- lα was seen mostly around the centrilobulalar veins by immunohistoehemistry findings. The liver HIF-lα protein was significantly higher in group of HAL than that of the controls after 3 days of the intervention [ （7.8 ± 3.2） % vs. （2.1 ± 1.4） % ], while the HIF-l α was increased evidently in group of BDL14 ＋ HAL in comparison with BDL7 ＋ HAL group at the 1 st day after the procedure[（ 8. 1±3.5 ） % vs. （3.5 ±2.3 ） % 3. Histological findings revealed a certain degree of liver cell degeneration and necrosis, inflammatory cell infiltration, small bile duct and collagen tissue hyperplasia in groups of HAL group and BDL ＋ HAL. Conclusion ： Obstruction of biliary tract should be managed before performing the ligation of hepatic artery in rats with biliary obstruction, hut that is capable of serious damage to liver function. The potential mechanism may be involved in the induced expression of HIF-1 α attributable to the establishment of collateral circulation after the procedure.