Effects Of The Extracts Of Fructus Canarii On Incipient Diabetic Nephropathy In STZ-induced Diabetic Rats

Objective: To investigate the influence of the extracts ofFructus Canarii through biochemical indexes and renal structure on incipientDiabetic nephropathy in STZ-induced Diabetic Rats and explore its potentialmechanism. Methods:①Reproduction of animal model and grouping:62SDrats were randomly divided into the diabetic nephropathy model group(n=50)and the control group(n=12). The rats in model group were intraperitoneallyinjected with streptozotion(STZ,65mg/kg), while those in control group wereinjected with equivalent dose of citric acid buffer solution. After1week of STZinjection,48rats whose FBG distributed between16.7mmol/L to28.2mmol/Lwere randomly divided into4group: model control group(M group, n=12),Lotensin(10mg/kg/d)(L group, n=12), low-dose extracts of Fructus Canarii(10mg/kg/d)(A group, n=12), high-dose extracts of Fructus Canarii(100mg/kg/d)(B group, n=12), respectively, plus normal control group(N group, n=12). Allrats were treated intragastrically for6weeks.②The detection of biochemicalindex (blood and urine samples): Concentration of blood BUN, SCr and24-hour urinary protein were tested with Urease method, Enzymatic method andend-point method respectively.③Kidney pathology: HE staining was used tofind pathological changes in kidney that were detected by optical microscopy.Immunohistochemistry and RT-PCR were used to test the expression of NF-κB and monocyte chemoattractant protein-1(MCP-1) in kidney, and ELISA wasused to detect the contents of ROS in kidney homogenate tissue.④Method ofstatistical analysis: SPSS19.0was used for date statistics. Dates were expre-ssed as average±standard deviation(x±s). P＜0.05was considered to besignificant. Results:①The change of weight: After rats were treated for6weeks, the weight between N group and model groups was significantlydifferent(P＜0.05), however there was no statistical difference between modelgroups.②The result of FBG: FBG of model groups were much higher than Ngroup, but there was no statistical difference between model groups.③Resultof renal function and24-hour urinary protein: BUN of model groups weremuch higher than N group(P＜0.01), and there was significant differencebetween B group and N group(P＜0.05). Compared with N group, SCr ofmodel groups were much lower than N group(P＜0.05), and there was nostatistical difference among SCr concentration of model groups (P＞0.05).Compared with N group,24-hour urinary protein increased significantly inmodel groups(P＜0.01), and compared with M group,24-hour urinary proteindecreased significantly in L group and B group(P＜0.05), and the decrease of Lgroup was more obvious(P＜0.01).④Morphology of kidney: The size ofmodel groups increased compared with N group, and the color was deeper. HEstaining showed glomerular volume increased, mesangial cells proliferated, partof the renal tubular epithelial cells degenerated like bubble and there wereinflammatory cells infiltration aroud renal tubular. L group and B group weremilder in above change, and L group was the mildest. A group and M group were heavier.⑤The contents of ROS in kiney tissue: Compared with N group,the contents of ROS in kiney tissue increased significantly in model groups (P＜0.01), while the contents of ROS in kiney tissue decreased significantly in Bgroup compared with M group(P＜0.05).⑥The mRNA and protein expressionof NF-κB and MCP-1in kidney: Compared with N group, the mRNA andprotein expression of NF-κB and MCP-1in kidney increased significantly inmodel groups(P＜0.01), and compared with M group, the mRNA and proteinexpression of NF-κB and MCP-1in kidney decreased significantly in L groupand B group(P＜0.05), and the decrease of L group was more obvious(P＜0.01). Conclusion:①The extracts of Fructus Canarii might reduce the renalinjury which showed glomerular volume increased, mesangial cells proliferated,part of the renal tubular epithelial cells degenerated like bubble in inciepientDiabetic nephropathy rats.②The extracts of Fructus Canarii might decreasedthe concentration of24-hour urinary protein of the inciepient Diabeticnephropathy rats.③The extracts of Fructus Canarii might reduce generation ofROS, and decrease the expression of NF-κB and MCP-1in the kidney ofincipient Diabetic nephropathy rats.④The extracts of Fructus Canarii mighttarget oxidative stress-inflammatory signaling, reduce renal injury, and delaythe development of Diabetic nephropathy through anti-inflammatory andantioxidant effect.