健脾清脂方治疗非酒精性脂肪性肝病肝郁脾虚证临床疗效及机制研究

Study on Clinical Efficacy and Mechanism of Jianpi Qingzhi Prescription in Treatment of Non-alcoholic Fatty Liver Disease with Liver Depression and Spleen Deficiency Syndrome

目的观察健脾清脂方治疗非酒精性脂肪性肝病(NAFLD)肝郁脾虚证的临床疗效,探讨其相关作用机制。方法采用随机数字表法将65例患者分为对照组32例和试验组33例。2组均予健康教育及对症支持治疗。对照组并予多烯磷脂酰胆碱胶囊,2粒/次,3次/d,口服;试验组并予健脾清脂方,150 mL/次,2次/d,口服。2组均连续治疗12周。比较2组临床疗效,检测2组治疗前后空腹血糖(FBG)、空腹胰岛素(FINS)、总胆固醇(TC)、三酰甘油(TG)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(γ-GT)及脂多糖、D-乳酸、二胺氧化酶(DAO)、紧密连接蛋白1(Claudin-1)、紧密连接蛋白4(Claudin-4)水平,观察2组肝/脾CT值及中医症状积分。结果对照组、试验组分别脱落2、3例。试验组总有效率为93.33%(28/30),对照组为80.00%(24/30),试验组明显优于对照组(P<0.05)。与本组治疗前比较,2组治疗后FBG、FINS、HOMA-IR、TC、TG水平明显降低(P<0.05);2组治疗后比较,试验组上述指标均明显低于对照组(P<0.05)。与本组治疗前比较,2组治疗后ALT、AST、γ-GT明显降低(P<0.05);2组治疗后比较,试验组上述指标明显低于对照组(P<0.05)。与本组治疗前比较,2组治疗后脂多糖、D-乳酸、DAO、Claudin-4明显降低,Claudin-1明显升高(P<0.05);2组治疗后比较,试验组脂多糖、D-乳酸、DAO、Claudin-4明显低于对照组,Claudin-1明显高于对照组(P<0.05)。与本组治疗前比较,2组治疗后肝/脾CT值明显升高,中医症状积分明显下降(P<0.05);2组治疗后比较,试验组肝/脾CT值高于对照组,中医症状积分低于对照组(P<0.05)。结论健脾清脂方可改善NAFLD肝郁脾虚证患者临床症状与体征,改善胰岛素抵抗和脂代谢紊乱,其机制可能是通过下调脂多糖、D-乳酸、DAO、Claudin-4水平并上调Claudin-1水平以提高肠道黏膜屏障功能,改善肝脏脂质沉积,提高肝功能。

Objective To observe the clinical efficacy and to explore the possible mechanism of Jianpi Qingzhi Prescription on non-alcoholic fatty liver disease(NAFLD)of liver depression and spleen deficiency syndrome.Methods Totally 65 patients with NAFLD were divided into control group(32 cases)and experiment group(33 cases)according to the random number table method.Both groups received health education and symptomatic supportive treatment.The control group was given polyene phosphatidylcholine capsules,2 capsules/time,3 times/d,orally;the experimental group was treated with Jianpi Qingzhi Prescription,twice a day,150 mL each time,orally.Both groups were treated continuously for 12 weeks.The clinical efficacy of the two groups was compared.Fasting blood glucose(FBG),fasting insulin(FINS),total cholesterol(TC),triglyceride(TG),liver function(ALT,AST,GT),lipopolysaccharide,D-lactate,diamine oxidase(DAO),Claudin-1,and Claudin-4 levels before and after treatment were detected.Liver/spleen CT value and TCM symptom scores of both groups were observed.Results The control group and the experiment group lost 2 and 3 cases respectively.The total effective rate of the experiment group was 93.33%(28/30),and the control group was 80.00%(24/30).The experimental group was significantly better than the control group(P<0.05).Compared with before treatment,FBG,FINS,HOMA-IR,TC,and TG in the two groups were reduced significantly(P<0.05);After treatment,the above indicators of the experiment group were significantly lower than those of the control group(P<0.05).Compared with before treatment,ALT,AST,andγ-GT were significantly reduced after treatment in the two groups(P<0.05);After treatment,the above indicators in the experiment group were significantly lower than those in the control group(P<0.05).Compared with before treatment,lipopolysaccharide,D-lactate,DAO,and Claudin-4 were significantly reduced after treatment in the two groups,and Claudin-1 increased(P<0.05);After treatment,D-lactic acid,DAO and Claudin-4 in the experiment group were significantly lower than the control group,and Claudin-1 was significantly higher than the control group(P<0.05).Compared with before treatment,the liver/spleen CT value of the two groups significantly increased after treatment,and the TCM symptom score significantly decreased(P<0.05);After the treatment,the liver/spleen CT value of the experimental group was higher than that of the control group,and TCM symptom score was lower than the control group(P<0.05).Conclusion Jianpi Qingzhi Prescription can improve the clinical symptoms and signs of NAFLD patients with liver depression and spleen deficiency,improve the insulin resistance and lipid metabolism disorder,and its mechanism may be through down regulating the levels of lipopolysaccharide,D-lactate,DAO and Claudin-4,up regulating the level of Claudin-1,improving the intestinal mucosal barrier function,liver lipid deposition and liver function.