养肝澳平合剂治疗肝纤维化的临床和实验研究
发布时间：2018-08-07 16:10
【摘要】：研究目的:临床研究方面,本课题评价养肝澳平合剂(YGAPM)治疗乙肝肝纤维化湿热瘀毒证的临床疗效;实验研究方面,制备四氯化碳/橄榄油诱导的大鼠肝纤维化模型,探讨YGAPM对肝纤维化模型大鼠的影响及可能机制。研究方法:1.临床研究60例慢性乙型肝炎(CHB)湿热瘀毒证患者,分为试验组30例,YGAPM联合恩替卡韦(entecavir,ETV)治疗,对照组30例,单用ETV治疗,观察6月,比较治疗前后中医证候积分、血清肝功能指标、血清肝纤维化指标、SWE值、APRI指数变化情况。2.实验研究将78只SD大鼠随机分为正常对照组(A组)、肝纤维化模型组(B组)、YGAPM高剂量组(C组)、YGAPM中剂量组(D组)、YGAPM低剂量组(E组)、秋水仙碱组(F组)。B、C、D、E、F组用CCL4/橄榄油腹腔注射法制备肝纤维化大鼠模型,在造模成功后,C、D、E组灌胃不同剂量的YGAPM,F组灌胃秋水仙碱,药物干预8周后采集血清及肝组织。采用生化方法测定大鼠肝功能、超氧化物歧化酶(SOD)、丙二醛(MDA)、羟脯氨酸(HYP)含量。免疫荧光法检测肝组织α-平滑肌肌动蛋白(α-SMA),转化生长因子β1(TGF-β1)。蛋白质印迹法检测TGF-β1、基质金属蛋白酶抑制剂-1(TIMP-1)表达。研究结果:1.临床研究两组CHB患者治疗前后比较,患者中医证候积分、血清肝功能指标(ALT、AST、ALP、GGT)、血清肝纤维化指标(HA、ⅣC、PCⅢ)、SWE值、APRI值均显著下降(P0.01,P0.05),试验组能明显改善患者临床症状:右胁疼痛、口干、口苦、腹胀、纳呆、尿黄、便秘、面色晦暗、唇紫、舌紫暗、苔黄腻等;改善部分肝功能指标(ALT、AST、ALP、GGT)及部分肝纤维化指标(HA、IVC);降低SWE均值、APRI值,较单用ETV有优势(P0.01,P0.05)。2.实验研究与B组比,药物干预各组肝功能水平均下降(P0.01),C组肝功能各指标下降显著(P0.01),与F组相比,差异有统计学意义(P0.05);药物干预各组肝脏组织MDA、HYP的含量明显降低(P0.01),而SOD含量明显上升(P0.01),C组较F组有统计学差异(P0.05,P0.01)。与A组比较,B组肝组织纤维化面积比例、α-SMA、TGF-β1、TIMP-1表达显著升高(P0.01),各药物干预组表达均显著下降(P0.01),C组更显著(P0.01)。研究结论:1.临床研究YGAPM联合ETV与单用ETV治疗乙肝肝纤维化湿热瘀毒证患者,两组均能明显改善患者临床证候,降低患者肝功能指标、肝纤维化水平、SWE均值、APRI指数。其中试验组在改善患者证候,部分肝功能指标(ALT、AST、ALP、GGT)及部分肝纤维化指标(HA、ⅣC),降低SWE均值、APRI值,较单用ETV组有优势。2.实验研究YGAPM能剂量依赖地降低肝脏损伤,改善肝纤维化。其抗肝纤维化机制可能是通过抗炎、抗脂质过氧化从而减少肝细胞损伤,间接降低胶原蛋白含量;并通过直接或间接抑制肝星状细胞(HSC)活化过程中的TGF-β1信号通路,逆转肝纤维化。
[Abstract]:Objective: to evaluate the clinical efficacy of Yanggan Aoping mixture (YGAPM) in the treatment of hepatitis B liver fibrosis with damp-heat and stasis toxin, and to establish a rat model of hepatic fibrosis induced by carbon tetrachloride / olive oil. To investigate the effect of YGAPM on hepatic fibrosis in rats and its possible mechanism. Research method: 1. 60 patients with chronic hepatitis B (CHB) with dampness-heat stasis and toxin syndrome were divided into experimental group (n = 30) treated with YGAPM combined with entecavirin (ETV) and control group (n = 30) treated with ETV alone for 6 months. The scores of TCM syndromes and serum liver function were compared before and after treatment. Serum hepatic fibrosis index SWE value and APRI index change. Seventy-eight SD rats were randomly divided into normal control group (group A), liver fibrosis model group (group B), high dose YGAPM group (group C), low-dose YGAPM group (group D), low-dose YGAPM group (E group), colchicine group (F group). The rat model of hepatic fibrosis was established by radiation method. Colchicine was administered to different doses of YGAPMN F group after successful modeling. Serum and liver tissue were collected after 8 weeks of drug intervention. The liver function and the content of superoxide dismutase (SOD),) malondialdehyde (MDA),) hydroxyproline (HYP) in rats were measured by biochemical method. 伪 -smooth muscle actin (伪 -SMA) and transforming growth factor 尾 1 (TGF- 尾 1) were detected by immunofluorescence assay. The expression of TGF- 尾 1 and matrix metalloproteinase inhibitor 1 (TIMP-1) were detected by Western blot. The result of the study was: 1. Before and after treatment, the scores of TCM syndromes, serum liver function index (alt) and hepatic fibrosis index (HA, 鈪，
本文编号：2170581
[Abstract]:Objective: to evaluate the clinical efficacy of Yanggan Aoping mixture (YGAPM) in the treatment of hepatitis B liver fibrosis with damp-heat and stasis toxin, and to establish a rat model of hepatic fibrosis induced by carbon tetrachloride / olive oil. To investigate the effect of YGAPM on hepatic fibrosis in rats and its possible mechanism. Research method: 1. 60 patients with chronic hepatitis B (CHB) with dampness-heat stasis and toxin syndrome were divided into experimental group (n = 30) treated with YGAPM combined with entecavirin (ETV) and control group (n = 30) treated with ETV alone for 6 months. The scores of TCM syndromes and serum liver function were compared before and after treatment. Serum hepatic fibrosis index SWE value and APRI index change. Seventy-eight SD rats were randomly divided into normal control group (group A), liver fibrosis model group (group B), high dose YGAPM group (group C), low-dose YGAPM group (group D), low-dose YGAPM group (E group), colchicine group (F group). The rat model of hepatic fibrosis was established by radiation method. Colchicine was administered to different doses of YGAPMN F group after successful modeling. Serum and liver tissue were collected after 8 weeks of drug intervention. The liver function and the content of superoxide dismutase (SOD),) malondialdehyde (MDA),) hydroxyproline (HYP) in rats were measured by biochemical method. 伪 -smooth muscle actin (伪 -SMA) and transforming growth factor 尾 1 (TGF- 尾 1) were detected by immunofluorescence assay. The expression of TGF- 尾 1 and matrix metalloproteinase inhibitor 1 (TIMP-1) were detected by Western blot. The result of the study was: 1. Before and after treatment, the scores of TCM syndromes, serum liver function index (alt) and hepatic fibrosis index (HA, 鈪，
本文编号：2170581
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