川芎嗪促进大鼠部分肝切除后修复性再生机制的研究

目的:探讨大鼠部分肝切除后肝功能的变化及川芎嗪对肝修复性再生能力的影响。方法:在相同月龄的动物中按体重均衡的原则随机分组。实验动物共分为5组:设正常对照组(对照组)、青年假手术对照组(假术组)、青年肝切除组(青切组)、中年肝切除组(中切组)和中年肝切除治疗组(切治组),每组动物10只,常规饲养,自由饮水。参照Higgins and Aderson给大鼠施行肝脏70%切除手术,中切组大鼠术前以川芎嗪(200 mg/kg/d)腹腔注射7d,其余组注射生理盐水。假术组大鼠以同样的手术程序打开腹腔但不施行肝部分切除术。各组施行手术动物在切除术后24 h沿腹中线切开动物腹腔,于腹主动脉两髂分支处取血分离血清,切取所有肝脏,待测。采用试剂盒法分别测定各组血清中丙氨转氨酶(ALT)、谷草转氨酶(AST)含量;肝脏匀浆后,采用八木国夫法检测肝组织中丙二醛(MDA)含量,采用western blot法测定肝组织中核增殖抗原(PCNA)和铜锌超氧化物歧化酶(SOD1)、锰超氧化物歧化酶(SOD2)的蛋白表达。结果:与中切组相比手术动物相比,切治组组大鼠血清中ALT、AST水平显著降低(P<0.05),肝细胞中PCNA表达显著升高(P<0.05),肝组织中MDA含量显著降低(P<0.05);肝组织中SOD1、SOD2表达显著增加。结论:肝脏切除70%后,肝功受损,氧化应激增加,但核增殖能力增强。川芎嗪可以抑制肝切手术导致的氧化应激损伤,促进SOD的表达,抑制MDA的升高,降低ALT、AST水平,提高PCNA的表达。提示中年大鼠肝切除后肝功能受损与氧化应激相关,给予抗氧化药物能够促进肝再生修复能力,青年肝切除手术大鼠肝的修复能力强于中年动物。

Study of the Facilitative Effect of Tetramethylpyrazine on Liver Repairing Regeneration of Rats after Partially Hepatectomy

Objective: To study the effect of tetramethylpyrazine on liver function and repairing regeneration after hepatectomy in middle-aged rats.Methods: 70 % lobe of liver was excised to establish animal model of hepatectomy in SD rats.50 SD rats were divided into 5 groups: including control group(A),sham operated group(B),hepatectomy in Young rats(C),hepatectomy in middle-aged rats(D) and treatment group of hepatectomy in middle-aged rats(E).Rats were subjected to 70 % partial hepatectomy(Higgins and Ander-son,1931).In E group,the animals were intraperitoneally injected with 200 mg/kg/d tetramethylpyrazine for a week before the operation,and animals in the other groups were injected with normal saline.24 h after the operation,the rats were sacrificed and serum and livers were collected.The content of Alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in serum was assayed.Western blot was used to detect the protein expression of proliferating cell nuclear antigen(PCNA) in livers.The content of malondialdehyde(MDA) and the protein expression of superoxide dismutase 1(SOD1) and superoxide dismutase 2(SOD2) were also measured in livers.Results: Compared with that of M group,serum ALT and AST in T group were significantly decreased(P <0.05);PCNA expression was evidently increased(P <0.05);the concentration of MDA in liver was markedly reduced(P <0.05);the expression of SOD1 and SOD2 were significantly increased.Conclusion: Tetramethylpyrazine could improve liver function and the capability of liver regeneration after hepatectomy in middle-aged rats,and the protective effect of tetramethylpyrazine may be due to the enhancement of antioxidant activity through the increase of SOD expression and the increased expression of PCNA.