| ObjectiveIn order to study the mechanism of Shenkang Injection(SKI)in protecting early diabetic nephropathy(DN),meta-analysis was used to analyze UAER,FBG,blood lipid,inflammatory factors and adverse reactions of SKI in early DN patients,and spontaneously modeled db/db mice were used to observe the effect of SKI on kidney function,glycolipid metabolism,insulin,inflammatory factors,pathological changes and the expression of JNK,IKK,IRS and PI3K.To clarify that SKI can protect DN by improving inflammation and alleviating insulin resistance,and provide new ideas for early intervention of DN and delaying the progress of renal function.Method1.Clinical Literature AnalysisThe Cochrane Library,EMBASE,Pubmed,Clinical Trials,China HowNet,Wanfang,Weipu and China Biomedical Literature Database were retrieved in recent 5 years.Chinese search terms included"Shenkang zhu she ye","Tang niao bing shen bing" and "Tang shen ";English search terms included "Shenkang Injection","SKI","Diabetic Nephropathy" and "DN".At the same time,manually retrieved textual research literatures in the literature.The methodological quality of the included articles was evaluated by referring to the bias risk assessment method of the Cochrane system evaluator manual.The data were analyzed by Revman 5.3.The aim of this meta-analysis is to evaluate the effect of Shenkang injection on improving urinary albumin excretion rate,FBG,TG,TC,TNF-a and IL-6.2.Animal experiment 20 8-week-old db/db mice were randomly divided into model group and Shenkang group according to random number table,10 mice in each group;8 healthy mice of the same age were taken as normal group.The mice in Shenkang group were intraperitoneally injected with Shenkang injection at 0.13ml/10g,and the normal group and the model group were intraperitoneally injected with normal saline at the same dose for 6 weeks,once a day.The weight and glucose of each mice were recorded during the experiment.The urine was collected in metabolic cage and the level of urinary microalbumin was detected.After 6 weeks of administration,all the mice undergoing the ITT,and finally orbital vein blood was taken for biochemical index detection,left kidney tissueswere weighed,1/2 kidneys were fixed with 4%paraformaldehyde for HE,PAS,'MASSOM and immunofluorescence detection,and the remaining kidneys were put into liquid nitrogen for the detection of inflammation and insulin resistance related pathways protein.Results1.Clinical literature analysisThe author included 16 randomized controlled trials with a total of 1402 patients.The literature is of medium quality.Meta-analysis showed that Shenkang Injection significantly decreased urinary albumin excretion rate(UAER)(mg24h-1 subgroup:MD=-50.09,95%CI[-71.77,-28.41],P<0.01;ug.min-1 subgroup:MD=-36.09,95%CI[-55.99,-16.19],P<0.01),as well as IL-6(MD=-9.81,95%CI[-17.37,-2.25],and CRP(MD=-2.02,95%CI[-3.42,-0.62],P=0.005),FBG(MD=-0.52,95%CI[-0.86,-0.19],P=0.002);as for TNF-a(MD=-9.38,95%CI[-21.23,2.47],P=0.12),TG(MD=-0.15,95%CI[-0.68,0.38],P=0.58),TC(MD=-0.73,95%CI[-3.42,-0.62],P=0.25)there was no significant difference.2.Animal experiment 1)At the 6th week of administration,the serum insulin,HOMA-IR and ITT level of model group mice was significantly higher than that of normal group and Shenkang group mice(p<0.01);2)The levels of IL-1,IL-6 and TNF-alpha in kidney homogenate of model group were higher than those of normal group,and the levels of inflammatory factors in Shenkang group were between the two groups,with no statistical significance;3)The urinary albumin level in Shenkang group was significantly lower than that of model group(p<0.01);the kidney index and urinary creatinine level in model group and Shenkang group were significantly lower than in normal group(p<0.01);the urinary creatinine level in Shenkang group was higher than that in model group(p<0.05);the serum urea nitrogen level in Shenkang group was significantly lower than that of model group(p<0.05);and the blood uric acid level in Shenkang group was significantly higher than that of model group(p<0.01);4)the blood sugar of Shenkang group mice was lower than that of model group mice(p<0.05),higher than that of normal mice(p<0.01);the levels of TG and NEFA of Shenkanggroup were lower than that of model group(p<0,05,P<0.01),but were significantly higher than the normal group(p<0.01);the content of CHO in Shenkang group was significantly higher than that of model group and normal group(p<0.01),and there was no difference between model group and normal group.5)In the model group,the epithelial cells of renal tubules showed vacuolar degeneration,and inflammatory cells infiltrated in the renal interstitium,glomerulus enlargement,diffuse proliferation of mesangial cells,moderate fibrosis of glomeruli and tubules,and the number of fibroblasts except cells decreased significantly,while in the Shenkang group relieved.The number of synaptopodin protein was less both in the model and Shenkang group than in the normal group.The level of podocin in shenkang group was higher than in model group(p<0.05),and the level of F4/80 was lower in model group(p<0.05).6)The expression of P-IKK beta,p-P50,p-JNK protein in model group increased,while that in Shenkang group decreased;compared with normal group,the levels of p-IRS1 S307 in model group increased,while those in Shenkang group decreased,and the expression of p-P85 in model group decreased compared with normal group while shenkang group increased.Conclusion1.Shenkang injection has a certain effect on improving urinary albumin excretion rate,IL-6,CRP and FBG in patients with diabetic nephropathy.It has no effect on TNF-a,TG and TC,but since thehighheterogeneity,more high-quality clinical trials are needed to verify it.2.Shenkang injection can reduce the excretion rate of urinary albumin in db/db mice with early diabetic nephropathy,and improve the metabolism of glucose and lipid and the histological morphology of kidney.3.SKI can improve insulin resistance by improving the level of kidney infla mmation in db/db mice with early diabetic nephropathy.Its mechanism is related to regulating JNK,IKKbeta and IRS/PI3K pathway. |
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