| Evidence-based research ObjectiveMany studies had found that the serum micro RNA-21 level of DKD patients was significantly different from those of DM patients and healthy people.However,there was no evidence-based medicine evidence.Therefore,this study intended to adopt the method of Meta analysis to explore micro RNA-The correlation between 21 and DKD provided a certain evidence-based basis for the future clinical application of micro RNA-21.MethodsComputers were used to search the Cochrane Library,Pub Med,EMbase,Ovid,CNKI,Wanfang Data,VIP and CBM databases to collect cross-sectional studies related to micro RNA and diabetic nephropathy.The search time limit was from the establishment of the database to May 2020.Two researchers independently screened the literature and extracted the data,and then used Stata 14.0software to conduct a Meta-analysis of the included indicators.ResultsA total of 9 cross-sectional studies were included,including 1051 subjects,including 513 in the DKD group,259 in the DM group,and 279 in the healthy group.Meta-analysis results showed that when the △△CT method was used to process the RT-q PCR test results,the expression of micro RNA-21 in the DKD group was higher than that in the DM group(P<0.05),and the expression of micro RNA-21 in the DKD group was higher than that of healthy people Group(P<0.05).ConclusionThe expression of micro RNA-21 in DKD was higher than that in DM and normal people,and it can be used as a biomarker for early diagnosis of DKD.Experimental research ObjectiveBased on micro RNA-21 and its downstream PTEN/PI3K/Akt/mTOR pathway,using db/db mice as an animal model to observe the effects of Jiangtang Sanhuang Tablet on the level of glucose and lipid metabolism,renal function,and urine protein levels in db/db mice.The pathological changes of kidney tissue and the impression of micro RNA-21 signaling pathway provided a certain experimental basis for its clinical application in order to explore the possible mechanism of Jiangtang Sanhuang Tablets in preventing and treating DKD.Methods32 7-week-old male db/db mice and 8 7-week-old male db/m mice were adaptively fed with ordinary diet for 1 week.According to the random number table method,32 mice were randomly divided into model groups and Jiangtang Sanhuang Tablets high-dose(JT-H)group,Jiangtang Sanhuang Tablets low-dose(JT-L)group and irbesartan group 4 groups.The experimental drug was intervened for 8 weeks.During the experiment,the general condition of the mice was observed.The weight,water intake,food intake,and fasting blood glucose of the tail tip were measured every 2 weeks.The 24-hour urine protein was measured before and 8 weeks after the medication.After the experiment,the mouse kidney function(CREA,BUN),lipid metabolism(CHOL,TG,HDL-C,LDL-C)were detected,and the pathological morphology of the mouse kidney was observed under light microscope.Western blotting was used to detect the expression of LC3 B,p62,PTEN,PI3 K,Akt,mTOR protein in the normal group,model group,JT-H group,and JT-L group,and RT-q PCR method was used to detect the expression of LC3 B,p62,and micro RNA-21 m RNA in the above four groups of mice.Results1.In terms of body weight,water intake,and food intake: in terms of body weight,after 8 weeks of treatment,the weight of the JT-H group decreased slightly compared to before treatment,and the weight of other groups increased to a certain extent,which was similar to the model group.In comparison,the weight of the JT-H group decreased significantly(P<0.05),and the weight of the JT-L group and the irbesartan group decreased slightly.The difference between the two groups was not statistically significant(P>0.05).In terms of water intake and food intake,after 8 weeks of treatment,compared with the model group,JT-H group and JT-L group decreased significantly(P<0.05),and JT-H group decreased more obviously than JT-L group,the difference was statistically significant(P<0.05),and there was no significant difference between the irbesartan group and the model group(P>0.05).2.In terms of glucose and lipid metabolism: After 8 weeks of treatment,compared with the model group,the blood sugar of the JT-H group and the JT-L group decreased(P<0.05),and the JT-H group decreased more obviously than the JT-L group,the difference was statistically significant(P<0.05),and there was no significant difference in blood glucose between the Irbesartan group and the model group(P>0.05).In terms of lipid metabolism,after 8 weeks of treatment,compared with the model group,the CHOL,TG,LDL-C of the JT-H group,the JT-L group and the Irbesartan group all decreased(P< 0.05).Among them,the CHOL and TG decreased more in the JT-H group,which was significantly different from the JT-L group and the Irbesartan group(P<0.05).3.Urinary protein and renal function: After 8 weeks of treatment,the normal group,the model group,the JT-H group,and the JT-L group all increased the urine protein,while the irbesartan group had a slight increase in urine protein.Compared with the model group,the JT-H and the JT-L increased less(P<0.05),and the difference was not statistically significant(P>0.05).The increase in the JT-H group was less than that in the JT-L group(P<0.05).In terms of renal function,after 8 weeks of treatment,compared with the model group,the levels of creatinine and urea nitrogen in the JT-H group,the JT-L group,and the irbesartan group were all decreased(P<0.05).Among them,the irbesartan group and the JT-H group decreased more significantly than the JT-L group,and the difference between the two groups was not statistically significant(P>0.05),and the difference between the JT-L group was statistically significant(P<0.05).4.Observation of kidney pathological morphology under light microscope:no pathological changes were seen in mice in the normal group,and the kidneys in the model group were severely affected.It can be seen that the glomerulus volume increased significantly,the renal capsule dilated,and the glomerular capillary plexus was unclear.The mesangium and basement membrane are thickened,accompanied by vacuolization of glomerular epithelial cells,and small vacuoles can be seen in the cytoplasm.Compared with the model group,the JT-H group,JT-L group and irbesartan group showed smaller lesions and milder lesions.5.Kidney LC3 B,p62,PTEN,PI3 K,Akt,mTOR protein expression: After 8weeks of treatment,the expression of LC3 B increased in the JT-H group and JT-L compared with the model group(P<0.05),the expression of p62 was reduced(P<0.05).Compared with the normal group,the JT-H group had no statistically significant difference in p62 expression(P>0.05).Compared with the model group,the expression of PTEN protein was up-regulated in the JT-H group and the JT-L group(P<0.05).Among them,the JT-H group was more significantly up-regulated.Compared with the JT-L group,the difference was statistically significant(P<0.05);the expression of PI3K/Akt/mTOR pathway protein decreased(P<0.05).Among them,the JT-H group decreased more significantly.Compared with the JT-L group,the difference was statistically significant(P<0.05).6.Kidney LC3 B,p62,micro RNA-21 m RNA expression: After 8 weeks of treatment,compared with the model group,LC3 B m RNA expression was up-regulated in the JT-H group and the JT-L group(P<0.05),p62 m RNA expression was down-regulated(P<0.05),and LC3 B in the JT-H group was up-regulated more significantly,and its expression was not statistically different from the normal group(P>0.05),and compared with the JT-L group.The ratio difference was statistically significant(P<0.05).Compared with the model group,the expression of micro RNA-21 was down-regulated in the JT-H group and the JT-L group(P<0.05).Among them,the JT-H group was down-regulated more significantly.Compared with the JT-L group,the difference was statistically significant(P<0.05).Conclusion1.In terms of evidence-based research,the expression of micro RNA-21 in DKD patients was higher than that in DM patients and normal people,and can be used as a biomarker for diagnosis of DKD.2.In terms of experimental research,Jiangtang Sanhuang Tablets can improve the general state of db/db mice,reduce blood sugar,regulate blood lipids,and improve glucose and lipid metabolism,and the effect of high dose is better than low dose.3.Jiangtang Sanhuang Tablets can reduce serum creatinine,urea nitrogen and urine protein in db/db mice,improve the pathology of the kidney tissue of db/db mice to a certain extent,and protect the kidney function of db/db mice.4.Jiangtang Sanhuang Tablets can up-regulate the expression of LC3 B protein and m RNA in db/db mice,and down-regulate the expression of p62 protein and m RNA,which can increase the level of autophagy in the kidneys of db/db mice,and the effect of high dose is better than low dose.5.Jiangtang Sanhuang Tablets can up-regulate the expression of PTEN protein in db/db mice,down-regulate the expression of PI3K/Akt/mTOR pathway related proteins,and down-regulate the expression of micro RNA-21 m RNA,and the effect of high dose is better than low dose.6.Jiangtang Sanhuang Tablets may activate PTEN by down-regulating the expression of micro RNA-21,thereby inhibiting the PI3K/Akt/mTOR pathway,initiating autophagy,and protecting the kidney. |
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