海兔素对刀豆蛋白A诱导的化学性肝损伤保护作用

Protective Effect of Aplysin on Chemical Liver Damage induced by Concanavalin A

目的:探讨海兔素对刀豆蛋白A诱导的化学性肝损伤保护作用。方法:雄性Wistar大鼠随机分为4组。模型组与海兔素组给予15 mg/kg刀豆蛋白A尾静脉注射每周一次,制作化学性肝损伤模型,模型制作成功后,正常对照组、模型组每日给予大豆油灌胃,海兔素低、高剂量组给予100、150 mg/kg·d海兔素+大豆油灌胃。实验持续8周后,禁食12 h,处死大鼠。HE染色观察肝组织形态学改变;Masson Trichrome及天狼星红染色观察肝组织纤维化状况;全自动生化分析仪检测血清ALT、AST及LDH水平;ELISA实验测定血清TNF-α和TGF-β1水平。结果:与正常对照组相比,模型组大鼠肝小叶结构模糊紊乱,纤维组织增生明显,可见灶状坏死及炎性细胞浸润,胶原纤维明显增多,胶原指数明显升高。血清中ALT、AST、LDH及TNF-α和TGF-β1水平显著升高(P<0.05)。海兔素干预后,肝小叶病变程度较模型组明显减轻,染色胶原显著减少,纤维增生明显改善,血清中ALT、AST、LDH及TNF-α和TGF-β1水平较模型组显著降低(P<0.05),海兔素高剂量组与低剂量组相比,肝脏病变改善程度更为明显(P<0.05)。结论:海兔素对刀豆蛋白A诱导的化学性肝损伤具有一定保护作用,其机制可能与下调TNF-α、TGF-β1水平有关。

Objective： To investigate the protective effect of Aplysin on chemical liver damage induced by the concanavalin A in rats. Methods： Forty male Wistar rats were randomly into four groups, control group,model group and low- and high-dose Aplysin treatment groups. The rats in model group, low- and high-dose Aplysin treatment groups were injected Con A at a dose of 15 mg/kg once a week for 8 weeks to establish the model of chemical liver damage, and the rats in control group were injected with nomal saline instead of Con A. The rats in control group and model group were given the soybean oil diet and the rats in low and high-dose Aplysin groups were treated with diet with 100, and 150 mg/（kg·d） Aplysin ＋ soybean oil once a day. The histopathological changes of liver was observed by HE staining, Masson trichrome staining and Sirius-Red staining; Olympus 400 automatic biochemical analyzer was utilized for detecting serum levels of ALT, AST and LDH; and the serum level of TNF-α and TGF-β1 was evaluated by ELISA method. Results： HE staining revealed that disorder hepatic lobules, inflammatory cellular infiltration and interstitial lymphocytic infiltration were found in model group. In low- and high-dose Aplysin treatment groups, the situation was getting better than that in model group. The result of Masson trichrome staining indicated that interstitial collagen tissue and staining collagen was increased in model group compared with the normal control group, and in low- and high-dose Aplysin treatment groups, the amount of staining collagen was significantly decreased compared with the model group（P〈0.05）. The result of Sirius-Red staining revealed that the amount of collagenous fiber was increased and pseudolobule was found in model group compared with control group, and in low- and high-dose Aplysin treatment groups,collagen fibrous proliferation was reduced compared with the model group. The serum levels of ALT, AST, LDH, TGF-β1 and TNF-αwere all increased in model group compared with the normal control group, while in high- and low-dose Aplysin groups, the serum levels of ALT, AST, LDH, TNF-α and TGF-β1 were all decreased（P〈0.05）, and the decrease of these indexes in high-dose Aplysin group was more obviously than that in low-dose Aplysin treatment group with statistical significance（P〈0.05）. Conclusions： Aplysin could in- hibit liver injury induced by concanavalin A, and its protective role might be related with the decrease of TGF-β1 and TNF-α level.