Study On The Characteristics Of Toxin Syndrome Elements Of Diabetic Kidney Disease And The Mechanism Of Jiedu Tongluo Yishen Concentrated Pill

Chapter 1: Study on The Characteristics of Toxin Syndrome Elements of Diabetic Kidney DiseaseObjective: To study the characteristics and correlation of clinical syndrome elements of toxin syndrome of diabetic kidney disease(DKD),and to construct the diagnostic criteria and syndrome differentiation points of toxin syndrome of DKD.Methods:1.Through literature research,sort out the types of symptoms related to DKD toxin syndrome,consult experts to screen out the pool of candidate symptom entries,define the symptom severity level of the entry(none,mild,moderate,severe),preliminarily define the criteria for judging toxin syndrome,and establish the clinical case information form of DKD toxin syndrome.A total of 300 patients(excluding 6 cases)were randomly divided into study group(221 cases)and verification group(73 cases).According to the preliminary criteria for judging toxic pathogen,the study group was divided into toxic evil syndrome group(n = 116)and non-toxic evil syndrome group(n = 105).2.By using statistical method,the symptom items were further screened from the aspects of sensitivity,differentiation and representativeness,the items were weighted by factor analysis,the threshold and the best diagnosis model were determined under the ROC curve,and the diagnostic standard scale model of DKD toxin syndrome was constructed.3.The DKD toxin syndrome diagnosis standard scale model was used to differentiate the syndrome of the study group and the verification group,and the sensitivity,specificity and Kappa value were calculated to evaluate the diagnostic ability of the scale.4.The clinical information of patients with DKD toxin syndrome diagnosis standard scale was collected,the characteristics of clinical syndrome elements of DKD toxin syndrome were analyzed,and the correlation between clinical data,physical and chemical examination of DKD patients and toxin syndrome was studied.Results:1.A pool of 44 symptom items was established,among which 14 items such as fatigue,edema,turbid urine,sore waist and knees,dizziness,purple tongue,dark complexion,limb numbness,loose stool,dry mouth,dry eyes,frequent nocturnal urination,abdominal distension and greasy coating were statistically significant.2.The diagnostic threshold was 140 DKD toxin syndrome differentiation criteria: total score = fatigue * 10 + edema * 10 + turbid urine * 10 + waist and knee soreness * 10 +dizziness of tongue * 10 + dark face * 9 + limb numbness * 8 + loose stools * 7 + dry mouth* 4 + dry eyes * 4 + frequent nocturnal urination * 3 + abdominal distension * 3 + greasy moss * 3.The degree of each item without this symptom should be multiplied by weight value by 0,mild by weight by 1,moderate by weight by 2,severe by weight by 3,and the total score ≥ 140 could be diagnosed as toxin syndrome.3.Evaluation result: In the study group,the sensitivity was 92.24%,the specificity was96.19% and the Kappa value was 0.882.In the verification group,the sensitivity was87.50%,the specificity was 96.97% and the Kappa value was 0.836.4.The characteristics of syndrome factors of DKD toxin evil syndrome were mainly blood stasis and yang deficiency,which were positively correlated(r > 0,P＜0.05).Other syndrome factors including qi deficiency,yin deficiency,blood deficiency,heat(fire),dampness,cold,wind,qi stagnation and phlegm were positively correlated with the course of disease,drinking,hyperuricemia and renal anemia.It was positively correlated with Hb A1 c,BUN,SCR,UA,cystatin C,e GFR and UACR(r > 0,P＜0.05).Conclusion: This paper constructs the diagnostic criteria of DKD toxin syndrome,and has good diagnostic ability,and makes clear the characteristics and correlation of syndrome elements of DKD toxin syndrome,which is closely related to syndrome elements such as blood stasis and Yang deficiency,and has a certain correlation with medical history data and physicochemical indexes,so as to provide a basis for syndrome differentiation diagnosis of DKD toxin syndrome.Chapter 2: Study on the Mechanism of Jiedu Tongluo Yishen concentrated PillObjective: In order to study the protective effect of Jiedu Tongluo Yishen concentrated pill on kidney under the guidance of professor Nan Zheng’s theory of "Toxin impairs kidney collaterals",and to explore its therapeutic mechanism.Methods:1.72 male SPF SD rats were fed adaptively for one week,and then the DKD rat model was induced by intraperitoneal injection of high fat diet combined with STZ.60 successful DKD rats were randomly divided into five groups(model group,high,middle and low dose groups of Jiedu Tongluo Yishen concentrated pills group,irbesartan group).High-dose3.0g/kg/d,medium-dose 1.5g/kg/d and low-dose 0.75g/kg/d were given to Jiedu Tongluo Yishen concentrated pill suspension,while 13.5mg/kg/d-dose irbesartan tablet suspension was given to the control group.After 8 weeks of intervention,the body mass,24-hour urine volume,glucose and lipid metabolism and renal function were recorded.2.The pathological changes of renal tissue in DKD rats were observed by light microscope.3.The expression of autophagy related proteins LC3,Beclin-1,p62 and podocyte injury related protein Nephrin,Podocin,WT-1 and AMPK/m TOR/Sirt3 pathway related proteins in renal tissue were detected by Westenblot.Results:1.The depression,weight loss,increased diet and increased urine volume of DKD rats treated with traditional Chinese medicine were alleviated.2.The levels of FBG,TC,TG,UAER,SCR,BUN and Cys-C in DKD rats treated with traditional Chinese medicine were significantly decreased.3.The pathological damage of kidney tissue structure of DKD rats treated with traditional Chinese medicine was improved.4.Increased expression of nephrin,podcin,WT-1,LC3II/LC3 I,Beclin-1,p-AMPK/AMPK,Sirt3 proteins and decreased expression of P62 p-m TOR/m TOR proteins in kidney tissue of DKD rats treated with traditional Chinese medicine.All of them were statistically significant.Conclusion: Jiedu Tongluo Yishen concentrated pill can improve somatic symptoms,regulate glucose and lipid metabolism,reduce urinary protein and protect kidney in DKD rats.It can up-regulate the expression of nephrin,Podcin,WT-1,LC3 and Beclin-1,down-regulate p62 expression,down-regulate p-m TOR/m TOR and up-regulate p-AMPK/AMPK and Sirt3.The mechanism may be related to the promotion of podocyte autophagy by AMPK/m TOR/Sirt3 pathway.