益气解毒通络颗粒对乙肝肝硬化患者肝星状细胞标记物VEGF和PDGF-AB的影响
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摘要
目的:探讨益气解毒通络颗粒剂治疗乙肝肝硬化好转的分子机制,完善该方治疗乙肝肝硬化的理论基础。方法:选取2015年6月至2017年10月在北京中医药大学东直门医院,采用简单随机化分组方法,随机选择符合入排标准的体检中心体检健康者15例,肝炎门诊就诊的乙肝肝硬化患者42例。乙肝肝硬化患者均已规范使用抗病毒药恩替卡韦分散片治疗,入组后予益气解毒通络颗粒治疗6个月;对健康者,乙肝肝硬化患者治疗前、治疗6个月后,分别采集血样,待标本集中后采用酶联免疫吸附法成批检测VEGF、PDGF-AB含量。并将测定结果进行统计分析。结果:结果显示,血清VEGF水平乙肝肝硬化患者治疗前较健康者轻度升高,治疗后较治疗前及健康者均有所下降,但组间比较无统计学意义(P>0. 05);血清PDGF-AB水平乙肝肝硬化患者治疗前较健康者显著降低(P <0. 001),治疗后较治疗前有所升高(P <0. 05)但仍低于健康者(P <0. 05)。结论:VEGF和PDGF-AB水平的变化与乙肝后肝硬化的发病相关,益气解毒通络颗粒能够改善乙肝肝硬化患者血清VEGF和PDGF-AB水平,这可能是其治疗乙肝肝硬化的作用机制之一。
Objective: To discuss the molecular mechanism of Yiqi Jiedu Tongluo Granules,which was used for treating patients with post-hepatitis B liver cirrhosis,and to provide the theory foundation for it. Methods: Cases were randomly selected from the visitors in Dongzhimen Hospital from June 2015 to October 2017 with 15 healthy persons of Medical Examination Center,and 42 patients with post-hepatitis B liver cirrhosis of Hepatitis clinic. The patients with post-hepatitis B liver cirrhosis had been treated by entecavir. The patients were treated with Yiqi Jiedu Tongluo Granules for 6 months; The serum of the healthy persons,the patients before treatment,and the patients after treatment was collected. The method of ELISA was used to detect the serum level of VEGF and PDGF-AB. Results: The serum level of VEGF in patients with post-hepatitis B liver cirrhosis was increased than those of healthy persons,and after-treating was decreased than before-treating. But the level of VEGF was not statistically significant among groups( P > 0. 05). The serum level of PDGF-AB in patients with post-hepatitis B liver cirrhosis was significantly decreased than those of healthy persons( P < 0. 001); after-treating was increased than before-treating( P < 0. 05),but was lower than those of healthy persons( P < 0. 05). Conclusion: The serum level of VEGF and PDGF-AB has some relativity with post-hepatitis B liver cirrhosis. Yiqi Jiedu Tongluo Granules can affect the serum level of VEGF and PDGF-AB,which may be one of its treatment mechanisms.
Objective: To discuss the molecular mechanism of Yiqi Jiedu Tongluo Granules,which was used for treating patients with post-hepatitis B liver cirrhosis,and to provide the theory foundation for it. Methods: Cases were randomly selected from the visitors in Dongzhimen Hospital from June 2015 to October 2017 with 15 healthy persons of Medical Examination Center,and 42 patients with post-hepatitis B liver cirrhosis of Hepatitis clinic. The patients with post-hepatitis B liver cirrhosis had been treated by entecavir. The patients were treated with Yiqi Jiedu Tongluo Granules for 6 months; The serum of the healthy persons,the patients before treatment,and the patients after treatment was collected. The method of ELISA was used to detect the serum level of VEGF and PDGF-AB. Results: The serum level of VEGF in patients with post-hepatitis B liver cirrhosis was increased than those of healthy persons,and after-treating was decreased than before-treating. But the level of VEGF was not statistically significant among groups( P > 0. 05). The serum level of PDGF-AB in patients with post-hepatitis B liver cirrhosis was significantly decreased than those of healthy persons( P < 0. 001); after-treating was increased than before-treating( P < 0. 05),but was lower than those of healthy persons( P < 0. 05). Conclusion: The serum level of VEGF and PDGF-AB has some relativity with post-hepatitis B liver cirrhosis. Yiqi Jiedu Tongluo Granules can affect the serum level of VEGF and PDGF-AB,which may be one of its treatment mechanisms.
引文
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[16]方玉强.血小板衍生生长因子在组织细胞再生和创伤修复的作用及其机制[J].国外医学创伤与外科基本问题分册,1997,18(1):1-3.
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[18]姜春霞.肾细胞癌组织中VEGF和PDGF的表达[J].肿瘤基础与临床,2015,28(6):480-482.
[19]Sobrevals L,Rodriguez C,Romero-Trevejo JL,et al. Insulin-like growth factor I gene transfer to cirrhotic liver induces fibrolysis and reduces fibrogenesis leading to cirrhosis reversion in rats[J]. Hepatology,2010,51(3):912-921.
[20]Grimmig T,Moench R,Kreckel J,et al. Toll Like Receptor 2,4,and9 Signaling Promotes Autoregulative Tumor Cell Growth and VEGF/PDGF Expression in Human Pancreatic Cancer[J]. Int J Mol Sci,2016,17(12):2060-2077.
[2]Lu FM,Zhuang H. Management of hepatitis B in China[J]. Chin Med J(Engl),2009,122(1):3-4.
[3]Wang FS,Fan JG,Zhang Z,et al. The global burden of liver disease:the major impact of China[J]. Hepatology,2014,60(6):2099-2108.
[4]科技部十二五重大专项联合课题组.乙型肝炎病毒相关肝硬化的临床诊断、评估和抗病毒治疗的综合管理[J].中华肝脏病杂志,2014,22(5):327-335.
[5]慢性乙型肝炎抗病毒治疗专家委员会.慢性乙型肝炎抗病毒治疗专家共识[J].中华实验和临床感染病杂志,2010,4(1):82-91.
[6]European Association for Study of Liver. EASL clinical practice guidelines. Management of chronic hepatitis B[J]. Gastroenterol Clin Biol,2009,33(6-7):539-554.
[7]Wang XB,Liu P,Tang ZP. Intervening and therapeutic effect of cordyceps mycelia extract on liver cirrhosis induced by dimethylnitrosamine in rats[J]. Chinese Journal of Integrated Traditional and Western Medicine,2008,28(7):617-622.
[8]Balsano C,Alisi A,Nobili V. Liver fibrosis and therapeutic strategies:the goal for improving metabolism[J]. Curr Drug Targets,2009,10(6):505-512.
[9]Domitrovi'c R,Jakovac H. Antifibrotic activity of anthocyanidin delphinidin in carbon tetrachloride-induced hepatotoxicity in mice[J].Toxicology,2010,272(1-3):1-10.
[10]Sobrevals L,Rodriguez C,Romero-Trevejo JL,et al. Insulin-like growth factor I gene transfer to cirrhotic liver induces fibrolysis and reduces fibrogenesis leading to cirrhosis reversion in rats[J]. Hepatology,2010,51(3):912-921.
[11]赫伟丽,徐光福.益气解毒通络方逆转肝纤维化的临床研究[C].上海:第14届全国中西医结合肝病会议,2010.
[12]Grünewald FS,Prota AE,Giese A,et al. Structure-function analysis of VEGF receptor activation and the role of coreceptors in angiogenic signaling[J]. Biochim Biophys Acta,2010,1804(3):567-580.
[13]高洁,王明国,李秀梅,等. PRF及所含三因子对大鼠脂肪干细胞增殖和黏附的影响[J].实用口腔医学杂志,2016,32(4):462-466.
[14]Siedlecki J,Asani B,Wertheimer C,et al. Combined VEGF/PDGF inhibition using axitinib inducesαSMA expression and a pro-fibrotic phenotype in human pericytes[J]. Graefes Arch Clin Exp Ophthalmol,2018,256(12):1-9.
[15]Andrae J,Gallini R,Betsholtz C. Role of platelet-derived growth factors in physiology and medicine[J]. Genes Dev,2008,22(10):1276-1312.
[16]方玉强.血小板衍生生长因子在组织细胞再生和创伤修复的作用及其机制[J].国外医学创伤与外科基本问题分册,1997,18(1):1-3.
[17]Russell R,Elaine W R,Daniel FB,et al. The biology of platelet-derived growth factor[J]. Cell,1986,46(5):155-169.
[18]姜春霞.肾细胞癌组织中VEGF和PDGF的表达[J].肿瘤基础与临床,2015,28(6):480-482.
[19]Sobrevals L,Rodriguez C,Romero-Trevejo JL,et al. Insulin-like growth factor I gene transfer to cirrhotic liver induces fibrolysis and reduces fibrogenesis leading to cirrhosis reversion in rats[J]. Hepatology,2010,51(3):912-921.
[20]Grimmig T,Moench R,Kreckel J,et al. Toll Like Receptor 2,4,and9 Signaling Promotes Autoregulative Tumor Cell Growth and VEGF/PDGF Expression in Human Pancreatic Cancer[J]. Int J Mol Sci,2016,17(12):2060-2077.