【摘要】：研究目的:臨床研究方面,本課題評(píng)價(jià)養(yǎng)肝澳平合劑(YGAPM)治療乙肝肝纖維化濕熱瘀毒證的臨床療效;實(shí)驗(yàn)研究方面,制備四氯化碳/橄欖油誘導(dǎo)的大鼠肝纖維化模型,探討YGAPM對(duì)肝纖維化模型大鼠的影響及可能機(jī)制。研究方法:1.臨床研究60例慢性乙型肝炎(CHB)濕熱瘀毒證患者,分為試驗(yàn)組30例,YGAPM聯(lián)合恩替卡韋(entecavir,ETV)治療,對(duì)照組30例,單用ETV治療,觀察6月,比較治療前后中醫(yī)證候積分、血清肝功能指標(biāo)、血清肝纖維化指標(biāo)、SWE值、APRI指數(shù)變化情況。2.實(shí)驗(yàn)研究將78只SD大鼠隨機(jī)分為正常對(duì)照組(A組)、肝纖維化模型組(B組)、YGAPM高劑量組(C組)、YGAPM中劑量組(D組)、YGAPM低劑量組(E組)、秋水仙堿組(F組)。B、C、D、E、F組用CCL4/橄欖油腹腔注射法制備肝纖維化大鼠模型,在造模成功后,C、D、E組灌胃不同劑量的YGAPM,F組灌胃秋水仙堿,藥物干預(yù)8周后采集血清及肝組織。采用生化方法測(cè)定大鼠肝功能、超氧化物歧化酶(SOD)、丙二醛(MDA)、羥脯氨酸(HYP)含量。免疫熒光法檢測(cè)肝組織α-平滑肌肌動(dòng)蛋白(α-SMA),轉(zhuǎn)化生長(zhǎng)因子β1(TGF-β1)。蛋白質(zhì)印跡法檢測(cè)TGF-β1、基質(zhì)金屬蛋白酶抑制劑-1(TIMP-1)表達(dá)。研究結(jié)果:1.臨床研究?jī)山MCHB患者治療前后比較,患者中醫(yī)證候積分、血清肝功能指標(biāo)(ALT、AST、ALP、GGT)、血清肝纖維化指標(biāo)(HA、ⅣC、PCⅢ)、SWE值、APRI值均顯著下降(P0.01,P0.05),試驗(yàn)組能明顯改善患者臨床癥狀:右脅疼痛、口干、口苦、腹脹、納呆、尿黃、便秘、面色晦暗、唇紫、舌紫暗、苔黃膩等;改善部分肝功能指標(biāo)(ALT、AST、ALP、GGT)及部分肝纖維化指標(biāo)(HA、IVC);降低SWE均值、APRI值,較單用ETV有優(yōu)勢(shì)(P0.01,P0.05)。2.實(shí)驗(yàn)研究與B組比,藥物干預(yù)各組肝功能水平均下降(P0.01),C組肝功能各指標(biāo)下降顯著(P0.01),與F組相比,差異有統(tǒng)計(jì)學(xué)意義(P0.05);藥物干預(yù)各組肝臟組織MDA、HYP的含量明顯降低(P0.01),而SOD含量明顯上升(P0.01),C組較F組有統(tǒng)計(jì)學(xué)差異(P0.05,P0.01)。與A組比較,B組肝組織纖維化面積比例、α-SMA、TGF-β1、TIMP-1表達(dá)顯著升高(P0.01),各藥物干預(yù)組表達(dá)均顯著下降(P0.01),C組更顯著(P0.01)。研究結(jié)論:1.臨床研究YGAPM聯(lián)合ETV與單用ETV治療乙肝肝纖維化濕熱瘀毒證患者,兩組均能明顯改善患者臨床證候,降低患者肝功能指標(biāo)、肝纖維化水平、SWE均值、APRI指數(shù)。其中試驗(yàn)組在改善患者證候,部分肝功能指標(biāo)(ALT、AST、ALP、GGT)及部分肝纖維化指標(biāo)(HA、ⅣC),降低SWE均值、APRI值,較單用ETV組有優(yōu)勢(shì)。2.實(shí)驗(yàn)研究YGAPM能劑量依賴地降低肝臟損傷,改善肝纖維化。其抗肝纖維化機(jī)制可能是通過(guò)抗炎、抗脂質(zhì)過(guò)氧化從而減少肝細(xì)胞損傷,間接降低膠原蛋白含量;并通過(guò)直接或間接抑制肝星狀細(xì)胞(HSC)活化過(guò)程中的TGF-β1信號(hào)通路,逆轉(zhuǎn)肝纖維化。
[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. 偽 -smooth muscle actin (偽 -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，

本文編號(hào)：2170581