CB1 and ERK gene expression in liver tissue of rats with experimental hepatic fibrosis
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摘要:
目的研究大麻素受体1(CB1)mRNA在肝纤维化形成过程中表达的变化,从基因转录水平探讨其与细胞外信号调节激酶(ERK)的关系。方法采用10%四氯化碳腹腔注射制备肝纤维化模型,分别于造模第2、4、6、8周留取小鼠的肝组织及血清。通过病理对肝组织进行形态学观察,荧光定量RT-PCR检测CB1 mRNA和ERK mRNA水平,生化法检测血清中ALT和AST的含量,放射免疫法检测血清中透明质酸(HA)的含量。结果与正常对照组相比,各模型组小鼠肝组织中CB1 mRNA和ERK mRNA含量显著升高(P<0.05),而且随造模时间的延长,CB1 mRNA和ERK mRNA含量亦逐渐增高,各组之间差异有统计学意义(P<0.05)。各模型组小鼠血清中ALT、AST及HA的水平随造模时间延长而不断升高,各组间差异具有统计学意义(P<0.05)。CB1 mRNA的含量不但与血清中ALT、AST、HA的含量呈显著正相关(r=0.741、0.763、0.769,P均<0.01),而且与肝组织中ERK mRNA含量也呈显著正相关(r=0.789,P均<0.01)。结论CB1可能通...
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关键词:
- 受体,大麻酚,CB1 /
- 细胞外信号调节MAP激酶素 /
- 肝硬化
Abstract:Objective To evaluate the roles of the cannabinoid receptor type 1 (CB1) and extracellular-signal regulated kinase (ERK) in hepatic fibrosis.Methods A rat model of hepatic fibrosis was generated by intraperitoneal injection of 10% carbon tetrachloride.Liver tissues and serum samples were collected at post-injection weeks 2, 4, 6, and 8.Histopathological changes were detected by hematoxylin-eosin staining.Changes in mRNA levels of CB1 and ERK were determined by quantitative reverse transcription-polymerase chain reaction.Biochemical assays were used to detect changes in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and radioimmunoassay was used to determine changes in serum hyaluronic acid (HA) level.Results Compared with the uninduced, non-fibrotic control group, the mRNA levels of CB1 and ERK were significantly higher in the fibrotic group at all times examined (all P<0.05) .Moreover, the levels of CB1 and ERK mRNA, and serum ALT, AST and HA significantly increased over time (all factors, all time points P<0.05) .The CB1 mRNA level in liver tissue was correlated with the levels of serum ALT, AST, and HA (r=0.741, 0.763, 0.769, respectively;all P<0.01) and with ERK mRNA in liver tissue (r=0.789, P<0.01) .Conclusion CB1 may promote the activation of ERK in rats with hepatic fibrosis, and may induce hepatic stellate cell proliferation via ERK signal transduction to promote progression of liver fibrosis.
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Key words:
- receptor /
- cannabinoid /
- CB1
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[1]Wasmuth HE, Trautwein C.CB1cannabinoid receptor antag-onism:a new strategy for the treatment of liver fibrosis[J].Hepatology, 2007, 45 (2) :543-544. [2]马宏宇.肝病患者血清中AST/ALT比值的临床意义[J].临床合理用药, 2010, 3 (21) :65-66. [3]马德佳, 何新发, 李燕妮.HA、PC-Ⅲ、Ⅳ-C及LN对肝纤维化的诊断价值[J].广西医学, 2011, 33 (3) :312-314. [4]Starowicz K, Nigam S, Di Marzo V.Biochemistry and phar-macology of endovanilloids[J].Pharmacol Ther, 2007, 114 (1) :13-33. [5]Caraceni P, Domenicali M, Giannone F, et al.The role of theendocannabinoid system in liver diseases[J].BaillieresBestPract Res Clin Endocrinol Metab, 2009, 23 (1) :65-77. [6]杨莉, 赵召霞, 侯军良, 等.大麻素受体1、FAK mRNA在小鼠肝纤维化形成过程中肝组织中表达及其相互关系[J].临床肝胆病杂志, 2011, 27 (8) :824-826. [7]Handra-Luca A, Bilal H, Bertrand JC, et al.Extra-cellularsignalregulated ERK-1/ERK-2 pathway activation in hu-man salivary gland mucoepidermoid carcinoma:associationto aggressive tumorbehavior and tumor cell proliferation[J].Am J Patho, 2003, 163 (3) :957-967. [8]Tsukada S, Parsons CJ, Rippe RA.Mechanisms of liver fi-brosis[J].Clin Chim Acta, 2006, 364 (1-2) :33-60. [9]Cudaback E, Marrs W, Moeller T, et al.The expression lev-el of CB1 and CB2 receptors determines their efficacy at in-ducing apoptosis in astrocytomas[J].PLoS One, 2010, 5 (1) :e8702. [10]Lotersztajn S, Julien B, Teixeira-Clerc F, et al.Hepatic fi-brosis:molecular mechanisms and drug targets[J].Ann-uRev Pharmacol Toxicol, 2005, 45:605-628.
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