| Diabetic kidney disease(DKD)refers to chronic kidney disease caused by diabetes,which is a common chronic complication of diabetes and an important cause of end-stage renal disease,which used to be called diabetic nephropathy(DN).In 2007,the National Kidney Foundation developed Kidney Disease Outcomes Quality Initiative(NKF/KDOQI),which recommended the replacement of DN with DKD for clinical diagnosis.Traditional Chinese medicine has advantages in treating DKD.In recent years,more and more attention has been paid to the treatment of DKD with "wind-drug".Based on Lv Renhe's theory of " micro abdominal mass",professor Zhao Jinxi proposed the pathogenesis theory of DKD " incubated wind in kidney collateral ",which suggest the treatment of DKD with Yiqiqufengtongluo recipe.How does this theory guide clinical practice? Why can it obtain good clinical curative effect after all? We conducted data mining on previous medical cases,and explored the possible mechanism of action through animal experiments,so as to provide data support and scientific basis for promoting the treatment of DKD with replenishing qi and dispelling wind to dredge collaterals.Purpose1?Through the data mining of the medical records,we sorted out the inheritance vein of the DKD " incubated wind in kidney collateral " pathogenesis hypothesis from professor Lv Renhe to professor Zhao Jinxi.It reveals the specific characteristics of the pathogenesis hypothesis of " incubated wind in kidney collateral " and the idea of "treating from wind" to guide the clinical diagnosis and treatment of DKD.2?Based on AMPK/mTOR signaling pathway mediated podocyte autophagy,animal experiments were conducted to explore the mechanism of replenishing qi and dispelling wind to dredge collaterals in the treatment of DKD.Methods1?By using descriptive statistics,support vector machine and other quantitative research methods,combined with the idea of qualitative research,data mining was conducted on the clinical cases of professor Lv Renhe and professor Zhao Jinxi.It systematically summarized the academic thought and experience inheritance characteristics of professor Lv Renhe and professor Zhao Jinxi treating DKD,and compared with the medical cases of the two doctors treating diabetes without DKD complications,so as to reveal the important role of replenishing qi and dispelling wind to dredge collaterals in the treatment of DKD diseases.2?By immunohistochemistry,western blot,realtime fluorescence quantitative PCR technique,we studied the effect of replenishing qi and dispelling wind to dredge collaterals recipe on the expressions of positive regulator AMPK and negative regulator mTOR of autophagy in DKD rat podocytes,as well as the downstream signal molecule ATG1 of AMPK/mTOR signaling pathway and the pore membrane protein Nephrin,Podocin and Desmin of podocytes,so as to explore the possible mechanism of treating DKD by replenishing qi and dispelling wind to dredge collaterals.Results1?(1)Among the 875 medical cases included,the frequency of qi deficiency syndrome in DKD medical cases was the highest(46.68%),followed by blood stasis syndrome(44.63%),and the frequency of wind-pathogenic syndrome was lower(2.21%).(2)All drugs in all medical cases were analyzed with different diseases and syndromes as the classification attribute,and the classification accuracy of SMO analysis was higher than that of ZeroR analysis.The SMO classification accuracy with "DKD" as the classification attribute was 84.86%,that with "qi deficiency" as the classification attribute was 76.31%,and that with "blood stasis" as the classification attribute was 72.71%.The SMO classification accuracy with disease as the classification attribute was higher than that with syndrome as the classification attribute.(3)The medical cases of Lv Renhe and Zhao Jinxi were analyzed respectively.In the SMO analysis with "DKD" as the classification attribute,the weight of qireplenishing drugs,promoting-circulation drugs and wind-dispelling drugs was relatively high.(4)The medical cases of Zhao Jinxi treating DKD were analyzed,and in the SMO analysis with Astragalus,Euonymus alatus,Rhizoma Dioscoreae Nipponicae and great burdock achene,the core drugs of replenishing qi and dispelling wind to dredge collaterals as classification attributes,the weight of DKD diagnosis was higher than that of each symptom,tongue and pulse.2?(1)24h urine protein: During the experiment,the increased value of 24 h urine protein was from high to low in the model group,western medicine group,TCM + rapamycin group,rapamycin group,sham operation group,TCM group and normal group(P=0.000),and the difference was statistically significant.(2)Blood glucose: After the successful modeling,except for the continuous drop of blood glucose in the TCM group,the blood glucose of the other three groups kept at a high level.The difference of blood glucose before and after intervention in the TCM group was statistically significant compared with that in the model group(P=0.001),western medicine group(P=0.000)and rapamycin group(P=0.006).(3)Renal function: The Scr level was from low to high in the sham operation group,TCM group,rapamycin group,model group,western medicine group,and TCM + rapamycin group(P=0.009).BUN level was from low to high in the sham operation group,TCM group,western medicine group,model group,rapamycin group,and TCM + rapamycin group(P=0.000).(4)Blood lipid: TG(P=0.001),CHO(P=0.000)and LDLC(P=0.000)in the TCM group were significantly lower than those in the model group,western medicine group and rapamycin group.(5)Liver function: ALT level from high to low was in the model group,rapamycin group,western medicine group,TCM + rapamycin group,TCM group,normal group,and sham operation group(P=0.000).AST level from high to low was in the model group,western medicine group,rapamycin group,TCM + rapamycin group,TCM group,normal group,and sham operation group(P=0.000).(6)Immunohistochemistry: Compared with the model group,the expressions of AMPK(P=0.973),ATG1(P=0.037),Nephrin(P=0.666),Podocin(P=0.465)in the renal tissue of rats in the TCM group were increased,while the expressions of Desmin(P=0.000)were decreased.(7)Western Blot: Compared with the model group,the expressions of Nephrin(P=0.018)and Podocin(P=0.342)in the renal tissue of rats in the TCM group were increased,while the expressions of mTOR(P=0.742)and Desmin(P=0.086)were decreased.(8)Realtime fluorescence quantitative PCR: Compared with the model group,the expressions of Nephrin mRNA(P=0.000),Podocin mRNA(P=0.000)in the renal tissues of rats in the TCM group were increased,while the expressions of mTOR mRNA(P=0.019)and Desmin mRNA(P=0.000)were decreased.Conclusion1?When professor Lv Renhe and Zhao Jinxi treated DKD,they emphasized the disease,syndrome and symptoms,especially the basic pathogenesis of the disease.The basic pathogenesis of DKD is qi deficiency,blood stasis,incubated wind in kidney collateral,and the basic treatment is replenishing qi and dispelling wind to dredge collaterals.The core drugs are Astragalus,Euonymus alatus,Rhizoma Dioscoreae Nipponicae and great burdock achene.The pathogenesis theory of DKD " incubated wind in kidney collateral " has important application value in guiding clinical practice.2?The recipe of replenishing qi and dispelling wind to dredge collaterals can reduce the 24 h urine protein,blood glucose and blood lipid in DKD rats,and protect their renal function and liver function.The specific mechanism may be to increase the expression of AMPK,ATG1,Nephrin and Podocin in the renal tissue of DKD rats,and reduce the expression of Desmin,which may promote the autophagy of renal podocytes,thus playing a role in protecting the kidney.In view of the multi-target effect of traditional Chinese medicine,the mechanism of treating DKD by replenishing qi and dispelling wind to dredge collaterals needs further study. |
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