Clinical Study On Yinchenhao Decoction In Treating Intrahepatic Cholestasis Of Pregnancy With Damp Heat Syndrome And Its Effect On Th17/Treg Balance

Objective(1)To compare the distribution of constitutional types of traditional Chinese medicine between patients with intrahepatic cholestasis of pregnancy and healthy pregnant women,explore the relationship between constitutional types of traditional Chinese medicine and the incidence of intrahepatic cholestasis of pregnancy,and provide a new theoretical basis for clinical prevention,diagnosis,treatment and nursing.(2)To study the effect of Yinchenhao Decoction on intrahepatic cholestasis of pregnancy from clinical efficacy,symptoms,serum biochemical indicators and perinatal outcomes,and to explore the pharmacological mechanism and clinical application value of Yinchenhao Decoction.(3)To compare the contents of immune indexes in patients with intrahepatic cholestasis of pregnancy and healthy pregnant women,and to explore the role of Th17/Treg in the pathogenesis of intrahepatic cholestasis of pregnancy.(4)To compare the changes of peripheral blood immune indexes in patients with intrahepatic cholestasis of pregnancy before and after treatment,to study the effect of Yinchenhao Decoction on Th17/Treg balance,and to explore the molecular mechanism of Yinchenhao Decoction in the treatment of intrahepatic cholestasis of pregnancy from the field of immunology.Methods1.Relationship between constitutional types of traditional Chinese medicine and ICP.1.1 Research object From April 2017 to March 2020,130 patients with intrahepatic cholestasis of pregnancy were selected as the study group,and 130 healthy pregnant women were selected as the control group.Inclusion criteria: 1)gestational weeks(> 28 weeks),single fetus and normal fetal development;2)meet the above ICP diagnostic criteria;3)gestational weeks can be determined according to the results of the last menstruation and B-mode ultrasonography;4)no other complications during pregnancy;5)patients and their families were included in the study and signed the consent of voluntary participation.1.2 Research method 130 patients with intrahepatic cholestasis of pregnancy and 130 healthy pregnant women were surveyed by “Personal Basic Data Questionnaire” and“Classification and Judgment Table of Constitution in Traditional Chinese Medicine”.The subjects answered 60 items of 9 sub-scales in the Chinese Medicine Constitution Classification and Judgment Table.Each question was scored at 5 levels,with the original score of 1-5 points.According to the different items,there was a reverse score(5-1 points).After answering all the questions,the original score and transformation score were calculated,and then the constitution type was determined.1.3 Observation index(1)Collect the general data of the research group and the control group,and make statistical analysis;(2)Contrast and analyze the results of TCM constitution classification between the two groups.(3)Logistic regression was used to analyze the correlation between TCM constitution classification and intrahepatic cholestasis of pregnancy.2.Clinical study of Yinchenhao Decoction on intrahepatic cholestasis of pregnancy and its effect on Th17/Treg balance.2.1 Research object 60 patients with intrahepatic cholestasis of pregnancy in our hospital from 130 ICP patients were selected and divided into observation group and control group on average,and 30 healthy pregnant women in the same period were selected as routine group.Inclusion criteria: 1)gestational weeks(>28 weeks),single fetus and normal fetal development;2)meet the above ICP diagnostic criteria;(3)gestational weeks can be determined according to the results of last menstruation and B-mode ultrasonography;(4)no other complications during pregnancy;(5)include patients and their families to know about the study and sign the consent of voluntary participation;(5)conform to the above ICP damp-heat.Syndrome differentiation criteria of Yun type;No ICP-related treatment was conducted before this study and no sex hormone-related drugs were used recently;Active cooperation with doctors in diagnosis and treatment and high compliance with the research intervention process(medication,review,etc.).2.2 Research method The basic data of three groups were collected,including living environment,work nature,education level,ICP history,etc.The subjects in the control group were treated with ursodeoxycholic acid orally for15mg/kg/day,a course of treatment for 14 days.The subjects in the observation group were treated with Yinchenhao Decoction,Yinchenhao Decoction(1 dose/day)and ursodeoxycholic acid(15mg/kg/day)on the basis of the control group,for a course of 14 days.The subjects in the routine group did not receive drug intervention treatment,and only routine pregnancy tests were carried out regularly.2.3 Observation index(1)The general data of the three groups were compared and analyzed,including age,gestational age,parity,ICP history,anxiety and depression,living environment,work nature,education level,etc.(2)The serum biochemical indexes of three groups before and after treatment were compared and analyzed: total bile acid(TBA),direct bilirubin(DBIL),total bilirubin(TBIL),alanine aminotransferase(ALT),aspartate aminotransferase(AST).(3)The contents of immune indexes(IL-17,TGF--β,IL-35)before and after treatment in three groups were compared and analyzed.(4)To compare the scores of skin pruritus and TCM syndromes before and after treatment between the observation group and the control group.(5)To compare the clinical effect between the observation group and the control group.(6)Comparing the perinatal outcomes of three groups of subjects(7)The risk factors of adverse perinatal outcomes were analyzed by logistic regression.Results1.Relationship between constitutional types of traditional Chinese medicine and ICP.(1)There was no significant difference in age,gestational age,parity,ethnic distribution,occupational nature,living environment and educational level between the study group and the control group(P > 0.05).(2)In the 130 healthy pregnant women in the control group,there were68 cases with mild state,accounting for 52.3%;among the 130 ICP patients in the study group,there were 10 cases with mild state,accounting for 7.7%.There was a significant difference between the two groups((P < 0.05);the study group was mainly distributed in three types of TCM Constitution,namely,damp heat,phlegm and blood stasis,66 cases(50.8%),24cases(18.5%),12 cases(9.2%).There was significant difference in the number of cases of the three constitution distribution between the two groups(P < 0.05).(3)Phlegm-dampness and damp-heat stasis were positively correlated with intrahepatic cholestasis of pregnancy(OR > 1,P < 0.05),and gentle quality may be a potential protective factor for intrahepatic cholestasis of pregnancy(OR < 1,P < 0.05).2.Clinical study of Yinchenhao Decoction on intrahepatic cholestasis of pregnancy and its effect on Th17/Treg.(1)There was no significant difference in general data between the observation group and the control group(P > 0.05).There was no significant difference in age,gestational age,parity,living environment,working nature and cultural level among the three groups(P > 0.05).The incidence of anxiety,depression and ICP history of the patients in the control group and the observation group were higher than those in the healthy routine group.The difference was statistically significant(P < 0.05).(2)Before treatment,the serum biochemical indexes(TBA,DBIL,TBIL,AST,ALT)of ICP patients were significantly higher than those of normal pregnant women,(P < 0.05).After treatment,the serum biochemical indicators(TBA、DBIL、TBIL、AST、ALT)of the observation group and the control group were improved compared with those before treatment,and there were significant differences(P < 0.05);the improvement of serum biochemical indicators(TBA、DBIL、TBIL、AST、ALT)of the observation group was better than that of the control group,and the data comparison between the two groups was significant difference between the two groups(P <0.05).(3)Before treatment,the serum levels of IL-17 in ICP patients were significantly higher than those of normal pregnant women.The serum levels of TGF-β,IL-35 in pregnant women were significantly lower than those in normal pregnant women(P < 0.05);After treatment,the expression of IL-17,in the observation group and the control group decreased significantly(P<0.05),and the expression of TGF-β,IL-35 in the observation group increased significantly(P <0.05),while the decrease of IL-17,and the increase of TGF-β,IL-35 in the observation group were greater than those in the control group.In the control group,there were significant differences in the levels of IL-17,TGF-β and IL-35 between the two groups after treatment(P < 0.05).(4)After treatment,the skin pruritus score of the two groups decreased compared with that before treatment,and the difference was statistically significant(P < 0.05).The decrease of the skin pruritus score of the observation group was significantly greater than that of the control group,and the difference between the two groups was statistically significant(P< 0.05).After treatment,the TCM syndrome scores of the observation group and the control group decreased to a certain extent,and the difference was statistically significant(P < 0.05);the scores of TCM syndromes in the observation group were significantly lower than those in the control group,and the differences between the two groups were statistically significant(P< 0.05).(5)After treatment,10 patients in the observation group were cured,12 patients were markedly effective and 7 patients were effective.The total clinical effective rate was 96.7%.In the control group,5 patients were cured,8 patients were markedly effective and 10 patients were effective.The total clinical effective rate was 76.7%.There was significant difference between the two groups(P<0.05).(6)After treatment,the number of cases of premature delivery,cesarean section,low birth weight infants,fetal distress and postpartum hemorrhage in the observation group were lower than those in the control group,and there was significant difference(P<0.05);There was no significant difference in perinatal outcomes between ICP patients and normal pregnant women in the observation group(P>0.05);Compared with healthy pregnant women in the control group,the number of premature delivery,cesarean section,fetal distress and postpartum hemorrhage in the control group was significantly higher than that in the conventional group,and the difference was statistically significant(P<0.05).(7)ICP history,anxiety and depression,TBA,ALT,AST,TBIL were correlated with adverse perinatal outcomes(OR > 1,P < 0.05).Conclusion(1)The constitution of TCM has a certain relationship with the occurrence of intrahepatic cholestasis in pregnancy.The damp-heat,phlegm-dampness and blood stasis are positively correlated with the occurrence of intrahepatic cholestasis in pregnancy.The gentle quality is the protective factor of intrahepatic cholestasis in pregnancy.It shows that pregnant women with damp-heat,phlegm-dampness and blood stasis constitution are more likely to cause intrahepatic cholestasis in pregnancy.In clinic,we can try to correct patients’ biased constitution by mediation and medication,and then prevent and treat ICP.(2)The expression of IL-17 in patients with intrahepatic cholestasis of pregnancy is higher than that in healthy pregnant women,and the expression of IL-35 and TGF-β is lower than that in healthy pregnant women.It suggests that Th17/Treg may participate in the pathogenesis of intrahepatic cholestasis of pregnancy by secreting related cytokines.(3)Yinchenhao Decoction may have a positive effect on regulating Th17/Treg balance,promoting more differentiation of initial CD4+T cells into Treg cells,increasing the expression of TGF-β and IL-35 in ICP patients,and reducing the expression of IL-17,enhancing the immunity of patients,thereby improving the symptoms and prognosis of patients.