川芎嗪促进大鼠部分肝切除后修复性再生机制的研究

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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。 Objective: To investigate the changes of liver function after partial hepatectomy in rats and the effect of ligustrazine on the repair ability of liver repair. Methods: The animals of the same age were randomly divided according to the principle of weight balance. The experimental animals were divided into five groups: normal control group (control group), sham operation control group (sham group), young liver resection group (Qingqie group), middle-aged liver resection group Hepatectomy group (control group), each group of 10 animals, routine feeding, free drinking water. According to Higgins and Aderson, 70% hepatectomy was performed in rats. Rats in the middle-dose group were injected intraperitoneally with tetramethylpyrazine (200 mg / kg / d) for 7 days, and the rest were injected with normal saline. Sham-operated rats opened the abdominal cavity with the same procedure but did not perform partial hepatectomy. Animals in each group were sacrificed 24 hours after resection of the abdominal cavity abdominal incision line, in the abdominal aorta Branch of the iliac iliac blood serum was collected, all the livers were taken for testing. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined by kit method. Malondialdehyde (MDA) content in liver tissue was detected by Yagi-Guofu method after liver homogenate, The protein expression of nuclear proliferative antigen (PCNA), copper and zinc superoxide dismutase (SOD1) and manganese superoxide dismutase (SOD2) in liver tissue. Results: The serum levels of ALT and AST were significantly decreased (P <0.05), and the expression of PCNA in hepatocytes was significantly increased (P <0.05) compared with that of the operation group MDA content was significantly lower (P <0.05); liver SOD1, SOD2 expression increased significantly. Conclusion: After hepatectomy 70%, liver function is impaired, oxidative stress is increased, but nuclear proliferation is enhanced. Tetramethylpyrazine can inhibit the oxidative stress injury caused by hepatectomy, promote the expression of SOD, inhibit the increase of MDA, decrease the level of ALT, AST and increase the expression of PCNA. It is suggested that the impaired hepatic function of middle-aged rats after hepatectomy is related to oxidative stress. Anti-oxidant drugs can promote the ability of liver regeneration and repair. The liver repair ability of young hepatectomy rats is stronger than that of middle-aged animals.
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