Research on the Mechanism of using Geniposide to improve the Free Fatty Acid Metabolism of Rats with Non-alcoholic Fatty Liver Disease

目的： 1.观察栀子苷改善非酒精性脂肪性肝病的效果； 2.从游离脂肪酸探讨栀子苷调节非酒精性脂肪性肝病的作用机制。 方法： 实验分两部分进行。 1.栀子苷改善大鼠非酒精性脂肪性肝病的药效学实验：将40只雄性大鼠随机分为正常组和造模组，分别给予普通饲料和改良后的高脂饲料喂养，4周后将造模组再随机分为模型组、栀子苷组及血脂康组，并给这4组老鼠分别灌胃给药或蒸馏水。观察一般情况，留取标本后记录并计算相应数据（体重、肝湿重、脂肪重），用相应方法检测肝组织TG、FFA，血清CHO、LDL-C、HDL-C的含量，及血清AST、ALT的活性。并观察肝组织肉眼及病理变化（HE染色），进行肝组织NAS...Objective 1. To observe the effectiveness of using geniposide to treat rats with NAFLD; 2. To examine the mechanism of using geniposide to intervene in NAFLD from FFA’s perspective. Method The experiment was divided into two parts. 1. Pharmacodynamics experiment to explore the effectiveness of using geniposide to treat rats with NAFLD: 40 male rats were randomly allocated to control group an...学位：医学硕士院系专业：医学院_中医内科学学号：2452012115323

栀子有效成分栀子苷的现代研究进展

目的对栀子苷的现代研究进展予以综述,以期为栀子苷的进一步研究及应用提供参考。方法综合近年来的相关文献,从栀子苷的分离提取工艺及含量测定、药理学与毒理学、药物代谢动力学等方面进行概述。结果栀子苷存在广泛的药理作用,但也有一定的毒性作用。结论有必要进一步探索栀子苷的用量控制和吸收方式以及毒性和保护作用的确切机制,运用现代科学的研究方式对其进行合理的利用与开发

栀子与茵陈蒿汤对非酒精性脂肪性肝病大鼠脂质代谢及血清酶学影响的比较

目的:观察比较栀子与茵陈蒿汤对非酒精性脂肪性肝病大鼠脂质代谢及血清酶学的影响。方法:用高脂饮食建立大鼠非酒精性脂肪肝模型,自造模第6周起,28只大鼠被随机分为模型组、栀子组、茵陈蒿汤组和易善复组,每组7只,灌胃饮用水或给药5周。通过肝脏组织HE染色观察肝组织病理学;肝功酶试剂盒及血脂试剂盒检测大鼠血清生化指标及肝组织甘油三酯(TG)含量。结果:模型组大鼠肝脏存在明显脂肪变性,并可见炎症细胞浸润,肝组织TG、血清总胆固醇(TC)、甘油三酯(TG)含量、血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)活性均显著升高(P<0.01),血清高密度脂蛋白胆固醇(HDL-C)含量显著降低(P<0.01);栀子组、茵陈蒿汤组大鼠肝脂肪变性及炎症反应较模型组明显减轻,肝组织TG、血清TG、TC含量、血清ALT、AST活性均较模型组显著降低(P<0.05,P<0.01),血清HDL-C则显著升高(P<0.01);栀子组在降低血清ALT及血清TC含量方面优于茵陈蒿汤组(P<0.05,P<0.01)。结论:栀子与茵陈蒿汤均能明显改善脂肪肝大鼠肝组织病理学变化,对非酒精性脂肪性肝病有较好的干预作用,而栀子在改善胆固醇代谢及抗炎症损伤方面,效果优于茵陈蒿汤

Efficacy of Zaozhu Yinchen Recipe for Treating Non-alcoholic Steatohepatitis and Its Effect on Free Fatty Acid and TNF-α

目的观察皂术茵陈方治疗非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)患者的临床疗效,并探讨其对游离脂肪酸(free fatty acid,FFA)及TNF-α的影响。方法采用随机数字表法将120例NASH患者分为治疗组及对照组,每组60例。治疗组予中药皂术茵陈方,每日1剂;对照组予水飞蓟宾葡甲胺片200 mg口服,每日3次,两组均治疗24周。分别于治疗前后通过检测血清ALT、AST活性及TC、TG水平;行腹部CT计算肝脾CT比值;应用肝组织病理检查评价非酒精性脂肪性肝病活动度积分(NAFLD activity score,NAS)及纤维化程度以评价临床疗效;并检测血清FFA及TNF-α含量。结果与本组治疗前比较,两组治疗后血清ALT、AST、TC、TG、FFA、TNF-α水平、肝组织NAS积分及症状体征积分均明显降低,肝纤维化程度明显改善(P<0.05,P<0.01),且治疗组降低更明显(P<0.05)。治疗24周后,治疗组肝纤维化分期总有效率及临床总有效率分别为80.00%(48/60)、85.00%(51/60),明显高于对照组[60.00%(36/60)、73.33%(44/60)],两组比较,差异有统计学意义(P<0.05,P<0.01)。结论皂术茵陈方可改善NASH患者的临床疗效,其作用可能与抑制血清FFA及TNF-α水平有关。Objective To observe the efficacy of Zaozhu Yinchen Recipe(ZZYCR) on non-alcoholic steatohepatitis(NASH) patients, and to explore its effect on serum free fatty acid(FFA) and tumor necrosis factor α(TNF-α).Methods Totally 120 patients with NASH were randomly assigned to the treatment group(60 cases,treated with ZZYCR, one dose per day) and the control group(60 cases, treated with Silibin Meglumine Tablets, 20 mg each time, thrice per day). The therapeutic course for all was 24 weeks. Serum levels of ALT and AST activities, TC and TG levels were detected before and after treatment. Peritoneal CT was performed in all patients, and CT ratios of liver and spleen calculated. NAFLD activity score(NAS) and degree of hepatic fibrosis were assessed using pathological examinations of liver tissue, and efficacy also evaluated. Serum contents of FFA and TNF-αwere also detected. Results Compared with before treatment in the same group, activities of ALT and AST, serum levels of TC, TG, FFA, and TNF-α, NAS, scores of symptoms and signs all obviously decreased, degree of hepatic fibrosis was obviously improved in the two groups(P < 0. 05, P < 0. 01). These changes were more obviously seen in the treatment group(P < 0. 05). After 24-week treatment, the total effective rate and total clinical efficacy were 80. 00%(48/60 cases) and 85. 00%(51/60 cases) in the treatment group, obviously higher than those in the control group [60. 00%(36/60 cases) and 73. 33%(44/60 cases) respectively], with significant difference(P < 0. 05, P < 0. 01). Conclusion ZZYCR could improve the clinical efficacy of NASH patients, and its mechanism might be associated with inhibiting serum levels of FFA and TNF-α.国家自然科学基金资助项目(No.81503529,81274155);; 福建省自然科学基金面上资助项目(No.2014J01374);; 福建省卫生厅中医药项目(No.wzpw201308);; 厦门市科技计划项目(No.3502Z20134020

皂术茵陈方治疗非酒精性脂肪性肝炎40例临床研究

目的:观察皂术茵陈方治疗非酒精性脂肪性肝炎的临床疗效。方法:将78例患者单盲法随机分为治疗组40例和对照组38例;治疗组予中药皂术茵陈方治疗,对照组采用水飞蓟宾葡甲胺片(西利宾安)治疗;两组均治疗2个月。检测治疗前后患者血清谷丙转氨酶(AlT)、谷草转氨酶(AST)活性、血清总胆固醇(TCH)、甘油三酯(Tg)含量;比较患者肝脏b超变化以及症状、体征积分等临床疗效。结果:经过2个月治疗,治疗组的临床总有效率达87.50%,较之对照组的73.68%,差异有统计学意义(P<0.05);两组治疗后症状、体征积分、肝脏b超改善情况、血清AlT、AST活性、血清TCH、Tg含量均较各自治疗前显著改善;较之对照组,治疗组上述改善更加显著(P<0.05)。结论:中药皂术茵陈方对改善非酒精性脂肪性肝炎有较好的临床疗效,可明显改善患者肝功能、血脂、b超影像指标及临床证候。国家自然科学基金(No.81274155); 福建省卫生厅中医药项目(No.wzpw201408); 厦门市重大科技计划项目(No.3502Z20100006

Mechanism of geniposide in improving free fatty acid metabolism in rats with non-alcoholic fatty liver disease

观察栀子苷改善非酒精性脂肪性肝病的效果,从游离脂肪酸探讨栀子苷调节非酒精性脂肪性肝病的作用机制。健康雄性Wistar大鼠40只,随机分为4组:正常组、模型组、栀子苷组和血脂康组,每组大鼠10只,正常组大鼠给予正常大鼠饲料喂养,其余3组大鼠均采用高脂饲料喂养以诱导非酒精性脂肪性肝病,造模时间为8周,从第5周起至第8周末,栀子苷组和血脂康组分别灌服相应的药物。记录大鼠体重、肝湿重、脂肪质量;用相应方法检测肝组织TG,FFA,FAS,AMPK,ACCase及Malonyl-Co A含量,血清CHO,LDL-C的含量,血清AST,ALT的活性;观察肝脏组织肉眼及病理变化(HE染色法)。结果显示,与正常组相比,模型组大鼠的体重;肝湿重;脂肪重;血清CHO,LDL-C,ALT,AST;肝组织TG,FFA,FAS,ACCase及Malonyl-Co A含量皆显著升高(P<0.01);肝组织AMPK活性显著降低(P<0.01),肝组织肉眼外观及病理切片脂肪变性明显,并出现炎症损伤;与模型组相比,栀子苷组大鼠体重、脂肪质量、肝组织FFA含量、血清ALT,AST活性均显著降低(P<0.01),肝湿重,肝组织TG,FAS,ACCase及Malonyl-Co A含量明显降低(P<0.05),肝组织AMPK活性明显增多(P<0.05),肝脏肉眼外观及病理学表现均有所改善;与模型组相比,血脂康组大鼠的肝湿重、脂肪质量、肝组织TG,FFA和血清LDL-C水平明显降低(P<0.05);与血脂康组相比,栀子苷组大鼠的体重、脂肪质量、肝组织FFA含量均显著降低(P<0.01),其他方面无明显差异。结果表明,栀子苷具有显著的改善高脂饮食诱导的大鼠非酒精性脂肪性肝病的药理效应;其改善大鼠非酒精性脂肪性肝病的游离脂肪酸代谢是通过调节"AMPK-ACCase-Malonyl-Co A-FFA"轴来实现的。To observe the effect of geniposide on non-alcoholic fatty liver disease( NAFLD),and discuss the mechanism of geniposide for NAFLD from the aspect of free fatty acid,forty healthy Wistar male rats were randomly divided into normal group,model group,geniposide and Xuezhikang group. The rats in normal group were fed with normal diets,and the rats in other 3 groups were given with high-fat diet for 8 weeks to induce the NAFLD models. From the week 5 to end of week 8,the rats in geniposide and Xuezhikang group were intervened with corresponding medicines. The body weight,liver wet weight,and fat weight of the rats were recorded.Visual and pathological changes in hepatic tissues were observed with HE staining. The contents of TG,FFA,FAS,AMPK,ACCase and Malonyl-Co A in hepatic tissue,contents of CHO and LDL-C in serum and activities of AST and ALT in serum were detected by using corresponding methods. The results showed that the body weight,liver wet weight,and fat weight of the rats,CHO,LDL-C,ALT and AST levels in serum,TG,FFA,FAS,ACCase and Malonyl-Co A levels in hepatic tissues of the rats in model group were significantly higher than those in normal group( P < 0. 01),while AMPK activity was significantly lower than that of the normal group( P < 0. 01),with obvious visual and pathological steatosis in hepatic tissues,and inflammatory injury occurred in model group. Compared with the model group,body weight of the rat,fat weight,levels of FFA in hepatic tissues,ALT and AST activities in serum,liver wet weight,TG,FAS,ACCase and Malonyl-Co A levels were significantly decreased in geniposide group( P < 0. 01),while the AMPK activity in hepatic tissues was significantly increased( P < 0. 05),with improvement in visual and pathological performance.Compared with the model group,liver wet weight,fat weight,TG and FFA levels in hepatic tissues,and LDL-C level in serum were significantly decreased in Xuezhikang group( P < 0. 05). Compared with Xuezhikang group,the body weight of rat,fat weight and FFA level in hepatic tissues were significantly lower in geniposide group( P < 0. 01),but with no significant difference in other aspects. These findings indicated that geniposide was highly effective in improving the pharmacological effect of NAFLD induced by highfat diet,and the mechanism was achieved through AMPK-ACCase-Malonyl-Co A-FFA axis.国家自然科学基金项目(81274155;81503529);; 福建省自然科学基金项目(2014J01374);; 福建省高等学校新世纪人才计划项目;; 厦门市科技计划项目(3502Z20134020);; 福建省中医药科研项目(WZPW201308

Study on the dose ratio of Chlorogenic acid-Geniposide to treat rats with experimental fatty liver based on uniform design

目的:运用均匀设计法优化绿原酸-栀子苷组合治疗实验性脂肪肝大鼠的最佳剂量配比,探讨中药有效成分配伍配比规律。方法:运用数学模型均匀设计法对绿原酸; -栀子苷组合中的2种中药有效成分进行分组设计,分为6种组合对高脂饮食诱导的实验性脂肪肝大鼠模型进行治疗,观察各组大鼠肝脏的病理变化,并以肝组织甘; 油三酯(TG)、血清低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、总胆固醇(CHO)、谷丙转氨酶(ALT)、谷草转氨酶(A; ST)测定作为筛选指标,优选二者的最优剂量配比,并根据所得重新分组验证。结果:与正常组比较,模型组脂肪肝大鼠肝组织TG、血清LDL-C、CHO含; 量明显升高(P<0.01),血清HDL-C含量明显降低(P<0.01),血清ALT、AST活性明显升高(P<0.01),肝组织存在明显脂肪变性。; 经多元逐步回归分析,绿原酸-栀子苷组合治疗脂肪肝的最佳剂量配比是绿原酸90mg+栀子苷90mg。结论:应用均匀设计与药效学分析的方法可有效优化中; 药有效成分组合的最佳剂量配比。Objective: To explore the active ingredients and dose ratio of medicine,; combined with the optimal dose ratio of Chlorogenic acid-Geniposide to; treat rats with experimental fatty liver. Methods: The active; ingredients and optimized prescription were screened out, adopting; uniform design to divide Chlorogenic acid-Geniposide into six; combinations, by using experiment on high fat diet-induced fatty liver; rat models, and the pathological results were observed. The serum LDL-C,; HDL-C, CHO, ALT, AST and liver TG were taken as the screening-indexes.; Results: Compared with the normal groups, the serum LDL-C, CHO, ALT, AST; and liver TG in model groups were significantly higher (P<0.01), the; serum HDL-C in model group was significantly decreased (P<0.01), and the; pathology of liver tissue got obvious steatosis. According to stepwise; regression analysis of uniform design, the best ratio of Chlorogenic; acid-Geniposide to anti-NAFLD were Chlorogenic acid 90mg with Geniposide; 90mg. Conclusion: Uniform design is the appropriate way to confirm the; optimized prescription for active ingredient of Chinese medicine.国家自然科学基金面上项目; 福建省自然科学基金面上项目; 福建省高等学校新世纪人才计划项

茵陈蒿汤调节高脂饮食诱导大鼠脂质代谢紊乱的作用机制

目的:探讨经方茵陈蒿汤调节高脂饮食诱导大鼠脂质代谢紊乱的作用机制。方法:将18只雄性SD大鼠随机分成正常组、模型组和茵陈蒿汤组,模型组和茵陈蒿汤组给予高脂饮食喂养10周,茵陈蒿汤组第6周起给予茵陈蒿汤灌胃5周。10周后处死大鼠,收集标本,检测血清甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、胆固醇(Ch)含量,肝组织TG含量,对肝脏组织进行HE染色。结果:茵陈蒿汤明显降低模型大鼠血清TG、LDL-C、Ch含量,增加血清HDL-C含量,显著降低肝脏TG含量,改善肝组织脂质沉积的病理状态。结论:茵陈蒿汤能够有效的调节高脂饮食诱导的大鼠血清和肝组织脂质代谢紊乱,其机制可能是促进HDL-C合成,减少Ch、TG、LDL-C在体内的蓄积