摘要
目的:探讨α-硫辛酸对实验性大鼠急性胰腺炎(acute pancreatitis,AP)并发肝损伤的抑制作用及机制.方法:采用3.5%牛磺胆酸钠逆行胰胆管注射制备急性胰腺炎大鼠模型,将♂Wistar大鼠54只,随机分为3组,假手术组(SO组,n=18)、急性胰腺炎组(AP组,n=18)、α-硫辛酸治疗组(ALA组,n=18),于造模后腹腔内注射α-硫辛酸(1mg/kg),各组以不同时间点3、6、12h分为3个亚组,每个亚组为6只大鼠.采用生化法测定血清的淀粉酶及肝功能ALT、AST水平;比色法测定肝组织中超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量;应用HE染色,观察胰腺、肝脏组织病理学变化,免疫组织化学法测定肝组织ICAM-1、VCAM-1蛋白的表达.结果:在AP组各时间点血清淀粉酶、ALT、SAT及肝组织中MDA含量均较SO组显著升高(3h:1525.17±370.36vs134.67±37.46,101.17±22.33vs35.40±5.71,62.71±19.16vs38.25±4.63,P<0.01;2.83±0.6vs2.12±0.41,P<0.05),而肝组织的SOD活力则明显降低(3h:43.12±5.87vs50.49±7.08,P<0.05),肝脏病理学可见以多处灶状坏死,伴大量炎性细胞浸润.在假手术组肝组织中几乎没有ICAM-1与VCAM-1的表达,而在AP组中则有较强的表达.与AP组相比,在ALA组血清淀粉酶、ALT、AST及肝组织MDA含量较AP模型组明显降低(3h:1141.50±617.01,78.11±15.50,47.16±12.25,2.37±0.48,P<0.05),SOD活力则明显升高(3h:45.36±5.67,P<0.05),肝脏病理学显示肝损伤改善,有少量肝细胞坏死,炎性反应明显减少;ICAM-1与VCAM-1表达明显减弱.结论:ALA对大鼠AP合并肝损伤有较好抑制作用,其机制可能与抗氧化作用以及抑制炎性细胞因子ICAM-1与VCAM-1的表达有关.
AIM：To explore the inhibitory effect ofα-lipoic acid（ALA）on hepatic injury in rats with acute pancreatitis（AP）.METHODS：A rat model of AP was established by retrograde injection of 3.5%sodium taurocholate into the biliopancreatic duct.Fifty-four Wistar rats（n=54）were randomly divided into three groups：sham-operation group（SO group,n=18）,acute pancreatitis group（AP group,n= 18）,and ALA treatment group（ALA group,n= 18）.The ALA group was intraperitoneally injected with 1 mg/kg ALA.Each group were further divided into 3 subgroups（n=6）for testing at 3,6 and 12 h after treatment.The levels of serum amylase,alanine aminotransferase（ALT）and aspartate aminotransferase（AST）were determined using an automatic biochemical analyzer.The SOD activity and MDA level in liver tissue were measured by colorimetry.Pancreatic gland and liver histological changes were evaluated by hematoxylin and eosin（HE）staining.The expression of ICAM-1 and VCAM-1 in liver tissue was determined by immunohistochemistry.RESULTS：The levels of serum amylase,ALT,AST and hepatic MDA at all time points were significantly increased（3 h：1 525.17±370.36 vs 134.67±37.46,101.17±22.33 vs 35.40±5.71,62.71±19.16 vs 38.25±4.63 and 2.83±0.6 vs 2.12 ±0.41,all P0.01 or 0.05）and SOD activity was decreased（3 h：43.12±5.87 vs 50.49±7.08,P 0.05）in the AP group compared with the SO group.Histological examination showed multifocal necrosis and inflammatory cell infiltration in the AP group.The expression of ICAM-1 and VCAM-1 in liver tissue was enhanced in the AP group,but was undetectable in the SO group.In the ALA group,the levels of serum amylase,ALT,AST and hepatic MDA were significantly decreased（3 h：1 141.50±617.01,78.11±15.50,47.16±12.25 and 2.37±0.48,all P0.05）and SOD activity was increased（3 h：45.36±5.67,P 0.05）compared with the AP group.Hepatic injury was improved and the expression of ICAM-1 and VCAM-1 was significantly decreased in the ALA group compared with the AP group.CONCLUSION：ALA exerts a protective effect against hepatic injury in rats with acute pancreatitis possibly by resisting oxidation and decreasing hepatic expression of ICAM-1 and VCAM-1.
出处
《世界华人消化杂志》
CAS
北大核心
2010年第25期2631-2636,共6页
World Chinese Journal of Digestology
关键词
Α-硫辛酸
急性胰腺炎
肝损伤
α-lipoic acid
Acute pancreatitis
Liver injury
