【摘要】 目的:研究血管紧张素Ⅱ(angiotens inⅡ,AngⅡ)受体拮抗剂对人肝癌HepG2小鼠移植瘤的抑制作用及对MMP-9mRNA表达的影响。方法:建立人肝癌HepG2小鼠移植瘤模型,采用灌胃的方法,用不同剂量的AngⅡ受体拮抗剂坎地沙坦进行干预,并设空白对照组。连续给药12 d后脱臼法处死小鼠,剥离瘤组织称重并计算抑瘤率;测血浆及肝组织中丙二醛(MDA)的含量;剥离脾脏及胸腺并计算脏器指数;用MTT法测小鼠脾淋巴细胞的增殖活性;采用逆转录-聚合酶链反应(RT-PCR)半定量法检测瘤组织中MMP-9 mRNA的表达。结果:坎地沙坦组能明显抑制HepG2移植瘤,抑瘤率可达11.3%;与空白对照组相比,模型组血浆及肝组织匀浆中MDA含量显著升高,干预组较模型组降低,差异有统计学意义(P<0.05);坎地沙坦各剂量组脾脏指数及胸腺指数明显升高,淋巴细胞增殖活性明显高于模型组,同时MMP-9 mRNA的表达低于模型组,差异有统计学意义(P<0.05)。结论:AngⅡ受体拮抗剂能影响小鼠淋巴细胞增殖过程,并对MDA及MMP-9mRNA的表达产生影响,从而可能对肝癌的发生、浸润、转移起一定的抑制作用。更多还原

【Abstract】 Objective:To explore the inhibitory function and the influence of MMP-9mRNA expression of the angiotensin Ⅱ receptor antagonist to the HepG2 rats model with xenograft of human hepatocellular carcinoma.Methods:we established the HepG2 rats model with xenograft of human hepatocellular carcinoma by means of the gastric gavage method.The different doses of angiotensin Ⅱ receptor antagonist candesartanwere given to the HepG2 rats model and the control group was made at random.Rats were sacrificed by dislocation with continuous administration of candesartan after 12 days and the tumor tissues were removed and weighed.The inhibitory rate to the tumor was detected,the level of malondialdehyde(MDA) was also detected in plasma and the liver tissue of the rats.The organ index and lymphocyte proliferation activity of rats spleen were measured using MTT method through removing the spleen and thymus of rats.The expression of MMP-9 mRNA in tumor tissue was detected by means of semi-quantitative method of reverse transcription-polymerase chain reaction(RT-PCR).Results:The candesartan could obviously inhibite the the HepG2 rats model with xenograft of human hepatocellular carcinoma and the inhibitory rate to the tumor was 11.3% in the group of candesartan administration and the MDA in the plasma and liver homogenates were significantly increased in the model group compared with the control group.The level of MDA decreased in the group of candesartan administration compared with the model group.There are significantly statistical differences between these two groups(P<0.05).The spleen index and thymus index significantly increased in the groups of candesartan administration and the lymphocyte proliferation activity was significantly higher than those of the model group and the level of MMP-9mRNA expression was significantly lower than those of the model group.There are also significantly statistical differences between these two groups(P<0.05).Conclusion:Angiotensin II receptor antagonist could affect the activity of lymphocytes proliferation and the level of MDA and MMP-9mRNA expression in rats.Angiotensin II receptor antagonist may inhibit the occurrence,invasion and metastasis of hepatocellular carcinoma at a certain extent.更多还原