Study On The Role And Mechanism Of Astragalus Against Mice With Cd-induced Diabetic Nephropathy

There are such complications combined with diabetes mellitus.Diabetic nephropathy(DN)is one of the common microvascular complications.DN has a complex pathogenesis,in which the role of environmental factors has become more and more obvious.Epidemiological studies have found that the environmental pollutant cadmium(Cd)may induce DN in the body,but the mechanism of action is not yet clear.Metabolomics can conduct a comprehensive and systematic study of the body's metabolites and has unique advantages in the study of DN.In this study,DN mouse model was induced by high fat and sugar diet combined with long-term intraperitoneal injection of low dose cadmium chloride.After verifying the cdn-induced model,the serum metabolites of the experimental mice were detected by metabolomics technology,and the potential biomarkers related to cdn-induced by astragalus were searched.Then from oxidative antioxidant levels in the body and the change of channel protein levels associated with markers to study the mechanism of action of radix astragali,in order to can provide some ideas on the prevention and treatment of DN and basis.(1)The establishment and verification of Cd induced DN mice modelDiabetic nephropathy mouse model was established by high fat and sugar diet feeding combined with intraperitoneal injection of cadmium chloride.The growth status and physiological indicators of mice in different experimental groups were observed,and the biochemical indicators and histomorphological observation of mice were detected,to make sure the model is built successfully.Experimental results show that the model of diabetic nephropathy group M fasting blood glucose in mice compared with normal control group K group showed rising trend,and kidney viscera coefficient is significantly higher than control group(**P<0.01),triglyceride,total cholesterol levels compared with K group produced a significant change(*P<0.05,**P<0.01),K group is significantly higher than low density lipoprotein content(*P<0.05),high density lipoprotein is showing a downward trend,also in the serum urea nitrogen and creatinine levels significantly higher than control group(**P<0.01,**P<0.01),urine creatinine levels significantly lower than that of K group(**P<0.01),urine trace albumin significantly higher than that of control group(**P<0.01),a series of physiological and biochemical indexes shows that high fat and sugar fed by intraperitoneal injection of joint damage in mice induced by cadmium chloride method.After administration of Astragalus membranaceus,the physiological and biochemical indexes such as body weight,organ coefficient,triglyceride,total cholesterol,low-density lipoprotein,serum creatinine,urine creatinine,and microalbumin were significantly improved.It can be shown that cadmium induce the body to produce diabetic nephropathy,while the jaundice have a protective effect on cadmium induced diabetic nephropathy.(2)Metabolic group analysis of Cd induced DN mice and astragalus protectionGC-MS and LC-MS was used to detect the serum of the mice in the different experimental groups.The metabolic profiles of the mice in the K,M,and H groups were analyzed using metabolomics methods to search for potential biomarkers.The results showed that the levels of triglyceride,galactosylceramide,LysoPC,and lithochemitin glycine conjugates in serum of group M increased to varying degrees compared with group K(*P<0.05,*P<0.05,*P<0.05,*P<0.05),sphingomyelin content was significantly higher than the control group(*P<0.05).After the treatment of astragalus,Leukotriene E3,Glycocholic acid,LysoPC(14:1(9Z))and PGP(18:0/22:5(7Z,10 Z,13Z,16 Z,19Z))showed a certain recovery trend.Changes in these potential biomarkers may be related to oxidative stress and inflammatory response.(3)The pathogenesis of Cd induced DN mice and the protective effect of astragalusDetection of different experimental mice kidney antioxidant index of superoxide dismutase(SOD),catalase(CAT),protein oxidation index hydroformylation,lipid peroxidation(PCO,MDA)and the inflammation factor of nitric oxide(NO).Results model M group kidney antioxidant index SOD significantly lower than that of K(**P<0.01),and the CAT also has a downward trend,the oxidation index PCO,MDA content were significantly higher than that of K(*P<0.05,**P<0.01),inflammatory factor K group is significantly higher than the NO content(*P<0.05);Given astragalus lavage after treatment,the activity of antioxidant index decline eased,rising a certain(#P<0.05),and oxidation index and the trend of increased levels of inflammatory markers were effectively restrain(##P<0.01).The expression levels of pi3k-akt signaling pathway proteins(PI3K,Akt,NF?B)and Nrf2 signaling pathway proteins(Nrf2 and Keap1)were detected in different experimental groups.The experimental results show that group M amount of PI3 K protein and Akt protein expression in the kidney compared with K produced obvious decline(*P<0.05,**P<0.01),and NF?B protein expression of predominate are obvious rise(**P<0.01);However,the expression of Nrf2 protein in M group decreased(**P<0.01),and the expression of Keap1 protein increased(*P<0.05).And after the astragalus membranaceus lavage protection,two pathways related proteins were produced different degree of expression quantity change trend,illustrates the astragalus can by changing these two signaling pathways related to oxidative stress and inflammation protein expression,to play a Cd DN mice kidney damage of protection.