The Effect And Mechanism Of Sangge Decoction On Diabetic Retinopathy

Part Ⅰ Meta-analysis of Ziyin Qingre Therapy for Diabetic RetinopathyObjective : To systematically evaluate the clinical efficacy of Ziyin Qingre method in the treatment of diabetic retinopathy by Meta-analysis.Methods : PubMed,Cochrane Library,Embase database,CBM database,China National Knowledge Infrastructure(CNKI),VIP and Wanfang Medical Database were searched on the Internet for all randomized controlled clinical trials of nourishing yin and clearing heat in the treatment of diabetic retinopathy from February 1,2012 to February 1,2022.According to the standard,the paper is included in the independent analysis by two commentators,and the Revman5.4 software is used for systematic evaluation.Results : A total of 28 studies involving 2442 patients were included.The total effective rate,visual acuity,TCM syndrome score,hemorheology,hemodynamics,macular thickness and adverse reactions of the control group treated with western medicine and the experimental group treated with Ziyin Qingre method were included in Meta analysis to explore the clinical efficacy of Ziyin Qingre method in the treatment of diabetic retinopathy.1 The clinical efficacy of the experimental group was significantly higher than that of the control group : OR = 3.34,95 % CI(2.68,4.16),Z = 10.76,P < 0.00001.2 The improvement of visual acuity in the experimental group was more obvious than that in the control group : MD = 1.31,95 % CI(0.62,2.00),P < 0.00001.3 Compared with the control group,the experimental group could effectively reduce the TCM symptom score : MD =-5.01,95 % CI(-7.36,-2.66),P < 0.00001.4 Experimental group compared with control group can effectively improve the hemorheology : whole blood high shear viscosity MD =-1.04,95 % CI(-1.18,-0.91),P < 0.00001;the whole blood low shear viscosity MD =-0.71,95 % CI(-1.39,-0.04),P< 0.00001;plasma viscosity MD =-0.34,95 % CI(-0.56,-0.12),P < 0.00001;hematocrit MD =-3.85,95 % CI(-8.17,-0.47 ],P < 0.00001.5 Experimental group compared with the control group can effectively improve hemodynamics : PI MD =-0.37,95 % CI(-0.48,-0.25),P < 0.00001;r I MD =-0.20,95 % CI(-0.31,-0.10),P < 0.00001;p SV MD = 2.46,95 % CI(2.16,2.76),P < 0.00001;e DV MD = 0.58,95 % CI(0.47,0.69),P < 0.00001;c RV MD =-1.45,95 %CI(-1.76,-1.15),P < 0.00001.6 Compared with the control group,the experimental group can effectively reduce the macular thickness : MD =-24.45,95 % CI(-45.85,-3.04),P < 0.00001.7 Experimental group compared with the control group can effectively improve fundus hemorrhage : MD =-0.87,95 % CI(-1.50,-0.24),P < 0.00001.8 There was no significant difference in the incidence of adverse reactions between the experimental group and the control group.Conclusion : The method of nourishing yin and clearing heat is effective in the treatment of diabetic retinopathy,and its clinical efficacy,visual acuity,TCM symptom score,hemorheology,hemodynamics,macular thickness and bleeding area are better than those of the control group,which has high clinical value.Part II Molecular Mechanism of Sangge Decoction in Treating Diabetic Retinopathy Based on Network PharmacologyObjective : To predict the mechanism of Sanggeying in the treatment of diabetic retinopathy based on network pharmacology.Methods : The main components of Sanggeyin were screened and retrieved by TCMSP database,and the potential component targets were screened by TCMSP platform.Combined with TTD database,Drugbank database,Dis Ge NET database,OMIM database,CTD database and Gene Cards database,the related disease targets were retrieved.The protein-protein interaction(PPI)network model was constructed using the protein interaction network analysis database(String),and the GO and KEGG pathways of the core targets were analyzed using the Metascape platform.Results : A total of 43 active components,250 targets and 90 targets for DR were screened from Sanggeyin.The enrichment analysis showed that the possible targets of Sangge Decoction were AKT1,TNF,ALB,TP53,CASP3,IL6,IL1 B,HIF1 A,JUN and PPARG,and the possible pathways were cancer pathway,TNF signaling pathway and NF-κB signaling pathway.Conclusion : Sanggeyin plays an indigenous role in the treatment of inflammatory response in diabetic retinopathy,which provides a theoretical basis for future experimental studies.Part III Study on the Preventive Effect and Mechanism of Sangge Decoction on Diabetic Retinopathy Based on TNF-α / NF-κB PathwayObjective : To study the effect of Sanggeyin on diabetic retinopathy in rats through animal experiments and preliminarily explore its possible mechanism.Methods : Sixty male SD rats were randomly divided into normal group,model group,high-dose Sangge group and low-dose Sangge group,with 15 rats in each group.After one week of adaptive feeding,the diabetic model was induced by intraperitoneal injection of streptozotocin(STZ)at 55 mg / kg.Sangge low dose group and Sangge high dose group were given Sangge drinking water decoction,respectively.The normal group and the model group were given the same amount of sterile water.The intragastric administration lasted for 12 weeks,during which the general state,weight and blood glucose of rats were recorded weekly.After the end of the experiment,the eyeball and retinal tissue were taken.The pathological changes of retina were observed by pathological sections of retina;q RT-PCR was used to detect the m RNA expression of TNF-α,IKKβ,IL1β and VEGF in retinal tissue;the expressions of TNF-α,IKKβ,p-NFκB p65,IL1β and VEGF in retinal tissue were detected by Western Blot.Results :1 General state : normal group rats during the general state of good,stable blood glucose,weight with the steady growth of age,crystal transparent;the blood glucose of rats in the model group was at a high level,thin,crystal opacity,and some cataracts appeared.Compared with the model group,the general state of rats in Sanggeyin low and high dose groups was improved to some extent,and the blood glucose and body weight were not statistically significant compared with the model group.2 Retinal tissue staining : Normal rat retina structure is similar to human retina structure,clear stratification,neat arrangement.The retinal cells in the model group showed vacuolar degeneration and disordered arrangement.Chinese medicine high dose,Sangge low dose group cells arranged neatly,rare cell edema.3 Effect of Sanggeyin on m RNA expression of TNF-α,IKKβ,IL1β and VEGF in retina :The contents of TNF,IKKβ,IL1β and VEGF in retina of model group were significantly higher than those of normal group(P < 0.05).The contents of TNF,IKKβ in retinal tissue of rats in high dose group and low dose group were significantly lower than those in model group(P < 0.05).VEGF in the retina of rats in the Sangge high-dose group was significantly lower than that in the model group(P < 0.05).4 Effect of Sanggeyin on the expression of TNF-α,IKKβ,p-NFκB p65,IL1β and VEGF protein in retina : Compared with normal group,the expression of TNF-α,IKKβ,p-NFκB p65,IL1β and VEGF protein in retina of model group increased(P < 0.01);compared with the model group,the contents of TNF-α,IKKβ,p-NFκB p65 and VEGF in the high-dose and low-dose Sangge groups were decreased(P < 0.01).Conclusion :1 A single intraperitoneal injection of streptozotocin(STZ)55mg / kg induced diabetic SD rat model of high success rate,low mortality,can be used as a basic experiment to explore the development and treatment of DR.2 Sanggeyin can act on TNF-α / NF-κB pathway,reduce IKKβ m RNA and protein content,inhibit NF-κB nuclear transfer,down-regulate VEGF and IL1β expression,prevent angiogenesis and chronic inflammation.