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目的探讨尾加压素Ⅱ受体(urotensinⅡreceptor,UT)拮抗剂Palosuran对四氯化碳(carbon tetrachloride,CCl4)诱导肝损伤大鼠的影响。方法 Wistar大鼠32只,随机分为对照组、4周模型组、8周模型组和治疗组各8只。4、8周模型组和治疗组腹腔注射体积分数40%CCl4+橄榄油的混悬液2mL/kg制备肝损伤模型,治疗组造模4周起给予Palosuran 300mg/(kg·d)灌胃连续4周;4、8周模型组造模成功后分别连续给予等量生理盐水灌胃4、8周;对照组腹腔注射等量生理盐水连续8周。实验结束后处死大鼠,切取肝脏同一部位,采用实时荧光定量PCR法检测4组肝组织尾加压素Ⅱ(urotensinⅡ,UⅡ)、UT mRNA相对表达量;心脏取血检测4组血浆UⅡ蛋白表达及血清谷丙转氨酶(glutamate pyruvate transaminase,GPT)、谷草转氨酶(glutamic-oxaloacetic transaminase,GOT)、总胆红素(total bilirubin,TBil)和白蛋白水平。结果肝组织UⅡmRNA、UT mRNA相对表达量、血浆UⅡ蛋白表达量在4周模型组[(5.47±1.06)、(3.27±0.54)、(79.13±3.78)ng/L]、8周模型组[(8.70±0.21)、(4.45±0.29)、(110.32±12.09)ng/L]和治疗组[(3.49±0.28)、(3.31±0.50)、(53.10±4.32)ng/L]高于对照组[(0.93±0.12)、(1.06±0.13)、(45.54±4.69)ng/L](P<0.05);4、8周模型组和治疗组血清GPT[(487.38±53.15)、(932.05±42.89)、(363.92±37.79)u/L]、GOT[(1 286.42±190.06)、(2 420.13±156.67)、(812.41±99.97)u/L]和TBil水平[(18.50±3.42)、(26.62±6.39)、(19.13±3.48)μmol/L]均高于对照组[(36.76±6.36)u/L、(95.33±5.92)u/L、(0.71±0.17)μmol/L](P<0.05),白蛋白水平[(28.38±2.67)、(28.83±2.39)、(27.63±1.83)g/L]与对照组[(31.06±3.03)g/L]比较差异无统计意义(P>0.05);4、8周模型组肝组织UⅡmRNA、UT mRNA相对表达量、血浆UⅡ蛋白表达量及GPT、GOT和TBil水平高于治疗组,8周模型组高于4周模型组(P<0.05);4、8周模型组和治疗组血浆白蛋白水平比较差异无统计学意义(P>0.05)。结论 UⅡ受体拮抗剂Palosuran可改善CCl4诱导的大鼠肝损伤,其机制与下调UⅡ和UT表达,抑制相关炎性因子释放有关。
Objective To investigate the effect of Palosuran, a antagonist of urotensin Ⅱ receptor, on hepatic injury induced by carbon tetrachloride (CCl4) in rats. Methods Thirty-two Wistar rats were randomly divided into control group, 4-week model group, 8-week model group and treatment group. 4, 8-week model group and treatment group intraperitoneal injection of a volume fraction of 40% CCl4 + olive oil suspension 2mL / kg model of liver injury, the treatment group from 4 weeks to give Palosuran 300mg / (kg · d) Week; after 4 and 8 weeks of model group success, they were given normal saline for 4 weeks and 8 weeks, respectively. The control group was given intraperitoneal injection of normal saline for 8 weeks. The rats were sacrificed at the end of the experiment, the same part of the liver was cut off, and the relative expression of urotensinⅡ (UⅡ) and UT mRNA in liver tissue was detected by real-time fluorescence quantitative PCR. The levels of UⅡ protein And glutamate-pyruvate transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), total bilirubin (TBil) and albumin. Results Compared with the model group [(5.47 ± 1.06), (3.27 ± 0.54), (79.13 ± 3.78) ng / L], the level of UⅡ mRNA, (4.70 ± 0.21), (4.45 ± 0.29) and (110.32 ± 12.09) ng / L, respectively, compared with those in the control group [(3.49 ± 0.28), (3.31 ± 0.50) and (53.10 ± 4.32) ng / (P <0.05). The GPT in the model group and the treatment group at 4 and 8 weeks were (487.38 ± 53.15) and (932.05 ± 42.89), respectively , (363.92 ± 37.79) u / L], GOT [(1 286.42 ± 190.06), (2 420.13 ± 156.67), (812.41 ± 99.97) u / L] and TBil levels [(18.50 ± 3.42), (26.62 ± 6.39, ), (19.13 ± 3.48) μmol / L] were significantly higher than those in the control group (36.76 ± 6.36 u / L, 95.33 ± 5.92 u / L, 0.71 ± 0.17 μmol / L, There were no significant differences in albumin levels between the two groups (P> 0.05). The levels of albumin in the control group [(28.38 ± 2.67), (28.83 ± 2.39) and (27.63 ± 1.83) g / The expression of U mRNA, UT mRNA, UⅡprotein, GPT, GOT and TBil were higher in the model group than those in the untreated group at 8 weeks (P <0.05); 4, Eight weeks model group and treatment group plasma albumin Level difference was not statistically significant (P> 0.05). Conclusion The UⅡreceptor antagonist Palosuran can improve CCl4-induced hepatic injury in rats. Its mechanism is related to down-regulation of UⅡ and UT expression and inhibition of the release of related inflammatory factors.