Professor Lv Renhe's Experience In Treating Diabetic Nephropathy With Qi-invigorating Method And Research On Its Kidney Protection Mechanis

BackgroundIn the past 30 years,with the rapid development of economy,China has become the first country in the world for diabetes mellitus.Diabetic kidney disease(DKD),as one of the important microvascular complications of diabetes,has become the leading cause of end-stage renal disease in China with its clinical features of persistent increased albuminuria excretion and/or progressive decrease in glomerular filtration rate.The pathogenesis of DKD is complex and there is a lack of specific drugs,while Chinese traditional medicine has significant efficacy in delaying the progression of DKD and improving the quality of life of patients.Therefore,it is important to actively explore the treatment methods and prescriptions of Chinese medicine to prevent and treat DKD,and to summarize the experience of famous Chinese medicine practitioners for the understanding of this disease.Professor Lv Renhe has been studying DKD for many years and has proposed the theory of "micro-accumulation",paying particular attention to the importance of the deficiency of benefiting qi in the pathogenesis of DKD.The study of the rules for the use of his benefiting qi method in the treatment of DKD and the inner mechanism of the effect of the core beneficial qi drugs will help improves the effectiveness and scientificity of the clinical application of the benefiting qi method in the treatment of DKD.ObjectiveThe clinical experience using the benefiting qi method of Professor Lv Renhe has summarized and explored in DKD through the collation of medical records,analy sis and data mining,and the intrinsic mechanisms of its renoprotective effects on DKD has explored,taking ginseng,a representative drug of the benefiting qi method,as an example.MethodsThe clinical study was based on retrospective case study,the original medical records were organized into an electronic database,and data mining was used to summarize the general information of patients,symptoms,and the frequency and frequency of the four natures of drugs,the five flavors,and channel tropism of drugs using SPSS software;association rules,Bayesian networks,and complex network analysis were used to analyze the common beneficial drugs and combinations of drugs at different stages of disease,and symptoms-drug regularity In order to explore Professor Lv Renhe’s clinical experience and medication ideas.The basic study was based on animal experiments,and the widely used type 2 diabetes mice model db/db mice were selected and randomly divided into model group,ginseng group and metformin group,with the same litter db/m as the normal group.The mice were tested for glucose,body weight,urine protein,lipids,renal function,inflammatory factors and oxidative stress indexes by colorimetric method and enzyme-linked immunosorbent assay,and the renal pathological changes were observed by using ematoxylin-eosin staining,periodic acid-schiff stain and Masson pathological staining.ResultsFor the clinical study:221 valid cases were included in this study,with a total of 82 patients.Among them,54 were males and 28 were females,the oldest age was 84 years old,the youngest was 28 years old,and the largest number of people in the age group of consultation was 61-70 years old.DKD stage was mainly G3bA2-A3 and G4A2-A3.The top 10 symptoms were:fatigue,foam in the urine,swelling of the lower extremities,increased nocturia,thirst,blurred vision,Diarrhea,back pain,sleeplessness,and spontaneous sweating.On the basis of Qi deficiency,concurrent symptoms are most common with Qi stagnation and blood stasis,stasis and blood blockage,and internal dampness and heat.Commonly used drugs to benefiting Qi are:licorice,prince’s ginseng(ginseng),astragalus,rhodiola,lingzhi,fried atractylodes;the four natures of drugs are mainly warm and calm,the five flavors are mainly bitter and sweet,and channel tropism of drugs are mainly heart,spleen and lung.In the association rule,the pairs of drugs with association rule relationship for benefiting Qi and invigorating Blood were found to be Huangqi and Angelica(confidence level 0.926);for benefiting Qi and invigorating Blood and dispersing symptoms were Chuanxiong and Lingzhi(confidence level 0.947);Chuanxiong and Ginseng(confidence level 0.878);Danshen and Ginseng(confidence level 0.841)Chuanxiong and Rhodiola(confidence level 0.833).The pairs of drugs that benefit Qi and nourish Yin were Ginseng,Mai Dong(confidence level 0.875),Licorice,Mai Dong(confidence level 0.813).In the plain Bayesian analysis,it was found that when princely ginseng,astragalus,and licorice were used as categorical attributes,they were most closely related to symptoms such as fatigue,swelling of the lower limbs,foam in the urine,and increased nocturia.Through complex network diagram and modular analysis,it was found that the core prescription consisted of seven drugs,Danshen,Chuanxiong,prince’s ginseng(ginseng),licorice,angelica,poria and red peony,which were in line with Lv Renhe’s medication ideas and medication habits.Using prince’s ginseng(ginseng)as a node,visualization analysis revealed that the drugs commonly paired with prince’s ginseng were danshen,Chuanxiong,peony skin,poria,poria,raw astragalus,angelica,zelenium,henna,citron,foxglove,sage,lingzhi,and rhodiola.For basic research:①The mice in the normal group had shiny hair,agile movement,long and lean body shape,and frequent activities.The mice in the model group,ginseng group and metformin group were obese,slow moving,less active,with more food and water intake,and the mice in the model group showed vertical hair,low body temperature and slow response to external stimuli in the late gavage period.In the ginseng and metformin groups,the trend of weight gain was slowed down,and the statistical difference was observed from the 6th week onwards.②After 8 weeks of pharmacological gavage intervention,compared with the blank group,model group mice had higher ACR and 6hUTP(P<0.01).Their renal pathology showed typical manifestations of diabetic nephropathy such as glomerular hypertrophy,the proliferation of thylakoid cells,expansion of thylakoid stroma,the proliferation of fibrous tissue,and extensive infiltration of inflammatory cells.Their serum TG、TC、GSP、BUN、MDA、ILla、IL-6、TNF-and 6hUTP(P<0.05),SOD,CAT were significantly decreased(P<0.05).Compared with the model group,the above indexes in the ginseng group were improved(P<0.05,P<0.01),and Scr levels of ginseng group were significantly reduced(P<0.01).Compared with the metformin group,there was no significant difference in the above indexes in ginseng group.Conclusions1.Professor Lv Renhe clinically attached importance to the application of benefiting qi method in the treatment of DKD,often combining other treatments such as invigorating blood,clearing heat and dispelling dampness on the basis of benefiting qi.The ginseng is the core drug for its application of the method of benefiting Qi,which often used together with bloodboosting drugs such as Radix Paeoniae,Salviae Miltiorrhizae and Peony Bark,and is included in the core prescription.The main components of "Hong Tai Ling Dan" and "Dangguibuxue Tang",which are commonly used by Prof.Lv for the treatment of DKD.Benefiting Qi method is the core and basic treatment method of Prof.Lv Renhe in treating DKD and should be emphasized.2.Ginseng,a representative drug of benefiting qi method,has good therapeutic effect on DKD model mice,which can improve renal pathological damage,regulate glucose and lipid metabolism,reduce urinary protein and protect renal function,while it also significantly improves the indexes related to oxidative stress and inflammatory response,and this may be a possible mechanism for its renal protective effect,which deserves further in-depth study in the future.