Effect and mechanism of ZaoZhuYinchenhao Decoction against Nonalcoholic steatohepatitis in rats based on the Endogenous Cannabinoid system

摘要 目的： 1.观察皂术茵陈方改善大鼠非酒精性脂肪性肝炎的效果； 2.从内源性大麻素系统探讨皂术茵陈方抗非酒精性脂肪性肝炎的作用机制。 方法： 实验分两部分进行。 1．皂术茵陈方改善大鼠非酒精性脂肪性肝炎的药效学实验：将40只雄性Wistar大鼠按照随机数字表法随机分成正常组、模型组、皂术茵陈方组和盐酸吡格列酮组。除正常组外，其它各组大鼠给予高脂饮食喂养12周，从第7周开始，给予对应的药物持续灌胃6周。实验结束后处死大鼠，收集肝脏和血清标本，并记录相应数据(体重、肝湿重)。用相应的生化检测方法检测肝组织匀浆ALT、AST活性、TG、T-CHO、HDL、LDL、MDA、SOD含量。...Abstract Objective: 1.Observe the pharmacological effect of using ZaoZhuYinchenhao Decoction to treat rats with non-alcoholic steatohepatitis; 2. To investigate the mechanism of action using ZaoZhuYinchenhao Decoction to improve the rats with non-alcoholic steatohepatitis based on the Endogenous Cannabinoid system. Method: The experiment was divided into two parts. 1. Pharmacodynamics of...学位：医学硕士院系专业：医学院_中医内科学学号：2452014115358

Principles for Formulating Prescriptions Based on Zang-Fu Organs,Origin and Superficiality,Deficiency and Excess,Cold and Heat Syndrome on guiding the clinical use of drugs on treatment of TCM liver diseases

《脏腑标本虚实寒热用药式》是张元素的代表作之一。张氏总结自己数十年的临床经验,阐述了以脏腑寒热虚实而言病机的学说,使得脏腑辨证说逐渐被后世医家所重视。该书中所记录的关于中医肝系疾病的处方用药方法简明扼要,既有对经典的继承也有个人的理论创新。把握五脏六腑生理,了解疾病病理发展,巧妙使用引经报使药物,从而达到提高药物疗效的目的,这一临床诊疗思路至今仍然具有指导作用。Principles for Formulating Prescriptions Based on Zang-Fu Organs,Origin and Superficiality,Deficiency and Excess,Cold and Heat Syndrome is one of ZHANG Yuansu＇s famous masterpieces.With decades of clinical experience,ZHANG Yuansu summarized his own pathogenesis theory corresponding to Zang-Fu organs,cold and heat syndrome,deficiency and excess syndrome.In his efforts,the theory of differentiation based on Zang-Fu organs was appreciated by doctors of later ages.Conciseness of the prescription and the medication rules on treatment of TCM liver diseases recorded in this book was the fruit of the combination of inheritance of the Classic and his own theoretical innovation.The clinical thought of diagnosis and treatment,including grasping physiological function of zang-fu organs,understanding progression of diseases,tactfully using medicines of guiding action and leading to improving the curative effects,is still of great clinical significance up to now.国家自然科学基金项目（No.81274155,No.81503529）; 福建省自然科学基金项目（No.2014J01374）; 厦门市科技计划资助项目（No.3502z20134020）; 福建省高等教育新世纪优秀人才支持计划项

对我国住房抵押贷款证券化的探讨

住房抵押贷款证券化是近几十年国际金融领域重大的创新工具之一。分析我国目前推行住房抵押贷款证券化的迫切性及其带来的各种积极效益,但是鉴于住房抵押贷款证券化在我国还属于新生事物,其产生与发展必然存在不少障碍,这主要体现在制度障碍和市场障碍上。最后,针对这些不利于证券化发展的因素,进而提出了相关的政策建议

Analysis of the relationship between gynecological diseases and tongue petechia

文章通过对舌诊在妇科疾病的应用分析,认为舌诊作为中医的重要诊法,是探讨脏腑内在状况的生物全息元的手段之一,在妇科临床诊断中具有重要作用。而经过王; 彦晖教授临床经验,加上在临床采集病例对照之后,笔者发现,在临床上妇科疾病出现舌尖瘀点的确较其它疾病高,值得我们日后作进一步的研究与探讨。Based on the analysis on the application of tongue diagnosis on; gynecological diseases, it was found that, as an important diagnostic; method in TCM, tongue diagnosis was one of the useful methods to explore; the biological holographic element of internal organs, which also played; an important role in clinical diagnosis of gynecologic diseases. With; professor WANG Yan-hui's clinical experience, and after comparison of; clinical cases, it was found that tongue petechia was concerned with; gynecological diseases, deserving of further research

Essence of tongue diagnosis of HE Meng-yao

岭南,指中国五岭以南的地区,相当于现在广东、广西及海南全境。因气候炎热潮湿,人群多脾胃虚弱,病多阳虚、痰湿。从晋代以后,当地医家以中原医学为基础; ,结合岭南特殊气候和人群体质特点,逐渐形成独具风格的岭南医学流派。何梦瑶作为岭南名医之一,其医术高明,医学著作颇丰,极大地促进了岭南医学的发展。; 《医碥》是其代表作之一,亦是其学术思想的精髓,为现代研究何梦瑶学术思想和岭南医家流派的主要古籍。其中所记载的舌诊方法,至今仍具有临床实用意义。Lingnan, Chinese refers to the south of the five ridges area, which is; equivalent to the current Guangdong province, Guangxi province and; Hainan province. All due to the hot and humid climate, majority of local; people are with spleen and stomach deficiency, most of the clinical; manifestation are yang deficiency and dampness. After the Jin dynasty,; based on the traditional Chinese medicine of central plains, the local; doctors gradually formed their unique medical schools, combining with; the characteristics of the local climate and peoples constitutions. As; one of the famous specialists in the south of the five ridges, HE; Meng-yao, greatly promote the development of local medical health level.; Yibian is one of his famous masterpieces, which is also the essence of; the his medicine. Records of tongue diagnosis in this book are still; practical in clinical.国家自然科学基金资助项目; 福建中医药大学校管课题; 福建省科技计划引导性项

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

Clinical Research of Kangshi Kangxian Recipe Treating on Hepatic Fibrosis of Chronic Hepatitis B

目的观察康氏抗纤方治疗慢性乙型肝炎肝纤维化的临床疗效,探讨其对肝组织N-花生四烯酸氨基乙醇(; arachidonoylethanolamine,AEA) 、2-花生四烯酸甘油( 2-arachidonoylglycerol,2-AG); 、大麻素受体1( cannabinoid receptor 1,CBR1) mRNA、大麻素受体2( cannabinoid receptor; 1,CBR2); mRNA含量变化的影响。方法将110例慢性乙型肝炎肝纤维化患者按随机数字表法分为治疗组和对照组,每组55例。治疗组予中药康氏抗纤方联合恩替卡韦分; 散片治疗,对照组用恩替卡韦分散片单药治疗,两组均治疗48周。判定两组临床疗效,检测血清ALT水平,HBV; DNA、HBsAg、HBsAb定量,肝组织病理、肝硬度变化,肝组织AEA、 2-AG含量和CBR1、CBR2; mRNA表达水平。结果与对照组比较,治疗组的临床总有效率、HBsAg阴转率、肝组织纤维化分期疗效有效率均高于对照组(chi~2 =; 4.453,4.152,6.364,均P < 0.05); 。与本组治疗前比较,治疗后两组患者肝纤维化瞬时弹性测定值、AEA、2-AG含量及CBR1、CBR2 mRNA表达均降低(均P <; 0.05),且治疗组降低更明显(均P < 0.05); 。肝组织病理显示:治疗后治疗组肝小叶结构基本完整,肝细胞轻度水样变性,汇管区纤维组织无增生,局部少量淋巴细胞浸润,炎症及纤维化较对照组明显改善。; 结论康氏抗纤方具有提高慢性乙型肝炎肝纤维化患者的临床总有效率、HBsAg阴转率、肝组织纤维化分期疗效有效率,其作用机制可能与调节内源性大麻素系统; 有关。Objective To observe the clinical effect of Kangshi Kangxian Decoction (; KSKXD) in treating on patients of hepatic fibrosis of chronic hepatitis; B ( CHB),and to explore the mechanisms of KSKXD by regulating the; contents of arachidonoylethanolamine ( AEA),2-arachidonoylglycerol (; 2-AG),cannabinoid receptor 1 ( CBR1 mRNA) and cannabinoid receptor 2 (; CBR2 mRNA) in the liver tissue. Methods Totally 110 patients with; hepatic fibrosis of CHB were assigned to the treatment group and the; control group according to random digit table,55 cases in each group.; The treatment group was treated with Chinese herb KSKXD combined with; Entecavir,and the control group was treated with Entecavir. Both of the; two groups were treated for 48 weeks. The clinical efficacy of the two; groups was determined. The serum ALT levels,HBV DNA, HBsAg and HBsAb; quantification,liver pathological changes,liver stiffness; changes,contents of AEA and 2-AG,mRNA expression of CBR1 and CBR2 in the; liver tissue were detected. Results The total effective rate,HBsAg; negative conversion rate,hepatic fibrosis staging and curative effect; rate of the treatment group were higher than those of the control group; (chi~2 = 4.453,4.152,6.364,allP <0.05). After treatment,the; instantaneous elasticity of liver fibrosis,the contents of AEA and; 2-AG,the mRNA expressions of CBR1 and CBR2 in the liver tissue in the; two groups were decreased compared to those of the same group before; treatment (P < 0.05),and the treatment group had better effect than that; of the control group (P < 0.05). The pathological changes in the; treatment group after treatment indicated the liver lobules; integrity,mild hydropic degeneration of liver cells,periportal fibrous; tissue hyperplasia,local small lymphocytic infiltration,which fibrosis; and inflammation were better than those of the control group.; Conclusions KSKXD was effective in the treatment of hepatic fibrosis of; CHB, which improved total effective rate,HBsAg seroconversion rate and; liver fibrosis stage efficiency. And its mechanism maybe related to the; regulation of the endocannabinoid system.国家自然科学基金资助项目; 福建省科技计划引导性项目; 厦门市科技惠民项目; 福建中医药大学临床专项校管课题基

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

苯硫酚对固氮酶催化活性的影响

研究了苯硫酚对棕色固氮菌固氮酶催化底物还原活性的影响。结果表明:当反应体系中固氮酶钼铁蛋白与苯硫酚的摩尔比为1:4时,固氮酶的乙炔还原活性比对照组下降了62.3％,下降的幅度随着苯硫酚浓度的升高而增大;但在乙炔存在的情况下,固氮酶的放H_2活性随着苯硫酚的浓度的升高而升高。在氩气氛下,苯硫酚浓度的升高对固氮酶放H_2活性的影响不明显。这一现象有可能是由于苯硫酚取代与铁钼辅基的Fe_1原子连接的半胱氨酸的巯基而引起的