g蛋白偶联受体激酶在大鼠肝星状细胞信号转导中作用及芍药苷对其影响-role of g protein-coupled receptor kinase in signal transduction of rat hepatic stellate cells and effect of paeoniflorin on it.docxVIP

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g蛋白偶联受体激酶在大鼠肝星状细胞信号转导中作用及芍药苷对其影响-role of g protein-coupled receptor kinase in signal transduction of rat hepatic stellate cells and effect of paeoniflorin on it.docx

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g蛋白偶联受体激酶在大鼠肝星状细胞信号转导中作用及芍药苷对其影响-role of g protein-coupled receptor kinase in signal transduction of rat hepatic stellate cells and effect of paeoniflorin on it

rhPDGF-BB 可能改变 HSC-T6 胞浆胞膜上 GRK2 蛋白的分布，使 HSC-T6 Gαi 蛋白偶联的信号通路激活，从而刺激了 HSC-T6 过度增殖。3. GRK2 抑制剂可明显抑制 rhPDGF-BB 诱导的 HSC-T6 胞浆蛋白中 GRK2 表达增加，促进 Gαi-1 和 Gαi-2 的表达的升高，而在胞膜蛋白中正好与此相反，同时可以升高细胞内 cAMP 水平，而 Pae 可能通过改变 GRK2 的表达和活性，恢复了 G 蛋白-AC-cAMP 信号通路的正常转导，从而抑制 HSC-T6 增殖、维持其正常功能。关键词免疫性肝纤维化；肝星状细胞；G 蛋白偶联受体激酶；血小板衍生生长因子；信号转导；芍药苷Role of G protein-coupled receptor kinase in signal transduction of hepatic stellate cells from rats with immunological hepatic fibrosis and the effects of paeoniflorinPH.M candidate:Li Rui Preceptor:Prof.Wei Wei(Institute of Clinical Pharmacology, Anhui Medical University，Key Laboratory ofAnti-inflammatory and Immunopharmacology of Education Ministry，Anhui Key Laboratory of Anti-inflammatory and Immunopharmacology，Anhui Engineering Technology Research Center of Anti-inflammatory and Immunodrugs，Anhui Key Laboratory of Research and Development of Chinese Medicine，Chinese Traditional Medicine Research Laboratory of Anti-inflammatory and Immuno-pharmacology，“115” Industrial Innovation Team in Anhui Province)ABSTRACTLiver fibrosis is a pathologic process that leads to deposition of an excess of extra cellular matrix (ECM), which is due to the synthesis of ECM exceeding the degradation of ECM. Pae is a principal active ingredient of total glucosides of paeony. Our previous study showed that TGP has anti-inflammatory, anti-oxidative, immunomodulatory, anti-hepatic injury and anti-immunological hepatofibrotic effects. The protein families of GPCR kinases (GRKs) play apivotal role in the process of desensitization of agonist-activated GPCRs.To further research of the antifibrotic treatment, the present study was designed to investigate the expression of GRK2 on porcine serum-induced liver fibrosis rats in vivo.In addition,the expression of GRK2 on HSC-T6 stimulated with recombinant hunman platelet drived growth factor-BB(rhPDGF-BB) were evaluated in vitro.Meanwhile,the effects of Pae on the expression of GRK2 and trarsmembra