PPAR-α激动剂WY14643对兔VX2肝癌MMP-9表达的影响

Effects of PPAR-alpha Agonist WY14643 on the Expression of MMP-9 in Rabbit VX2 Hepatocellular Carcinoma

目的:研究过氧化物酶体增殖物激活受体-α(PPAR-α)激动剂WY14643对肝细胞癌血清基质金属蛋白酶-9(MMP-9表达的作用。方法:建立兔VX2肝癌模型24只,将其随机分为4个组,即对照组、低剂量组、中剂量组、高剂量组,每组6只,各给药组分别经耳缘静脉给予低剂量(1 mg/kg)、中剂量(3 mg/kg)、高剂量(6 mg/kg)WY14643,对照组给予同等体积的0.9%氯化钠溶液(NS),分别测定各实验组给药前及给药后12、24、48 h血清中MMP-9的含量,对照组同期抽血检测,采用SPSS 22.0进行统计学分析。取血后处死实验动物,获取肿瘤组织及癌旁肝组织离体标本,进行组织病理检查。结果:与对照组比较,WY14643中、高剂量组血清MMP-9的含量明显降低,差异有统计学意义(P<0.05)。4组肿瘤组织细胞均呈明显病理改变;对照组及低剂量组癌旁肝组织可见大量脂肪变性和凋亡细胞,周围组织内大量炎性细胞浸润,中、高剂量组癌旁肝组织仅见轻度脂肪变性及少量炎性细胞浸润。结论:WY14643对兔VX2肝癌MMP-9具有一定的抑制作用。

Objective:To study the effect of PPAR-alpha agonist WY14643 on the expression of MMP-9 in hepatocellular carcinoma.Methods:Twenty-four rabbits with VX2 hepatocellular carcinoma were established and randomly divided into four groups:the control group,the low,the medium and the high dose group,each group consisting of 6 rabbits.Each medicated group was given WY14643 at low(1 mg/kg),medium(3 mg/kg)and high(6 mg/kg)doses via ear vein respectively.The control group was given the same amount of 0.9%sodium chloride solution(NS).The levels of MMP-9 in serum of each medicated group were determined before and 12,24 and 48 hours after administration.The control group was detected by blood sampling at the same time,and the SSPS 22.0 was used for statistical analyses.Then the experimental animals were killed and the samples of tumor tissues and adjacent liver tissues were obtained for histopathological examination.Results:Compared with the control group,the serum levels of MMP-9 in WY14643 medium and high dose groups were significantly lower(P<0.05).The tumor cells in the four groups showed obvious pathological changes;in the control group and the low dose group,a large number of steatosis and apoptotic cells were observed in the liver tissues adjacent to cancer,and a large number of inflammatory cells infiltrated in the surrounding tissues.Only mild steatosis and a small number of inflammatory cells infiltrated in the liver tissues adjacent to cancer in middle and high dose groups.Conclusion:WY14643 has a certain inhibitory effect on MMP-9 of VX2 hepatocellular carcinoma in rabbits.