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Renal Protective Effects And Mechanism Of Uremic Clearance Granule On Contrast-induced Nephropathy

Posted on:2015-11-25Degree:MasterType:Thesis
Country:ChinaCandidate:W F DingFull Text:PDF
GTID:2284330422976944Subject:Internal Medicine
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Objective:To explore the efficacy and mechanism of Uremic Clearance Granule oncontrast-induced nephropathy(CIN), by observing renal function and pathology andthe expression of kidney injury molecule-1(KIM-1)、nuclear factor-κB (NF-κB) andtumor necrosis factor-α (TNF-α) in the renal tissue of rats subjected to CIN.Methods:The CIN rat model will be made by tail vein injection of iodinated contrast agents.One hundred forty-four adult male Sprague-Dawley rats with mean of weight250±50g were randomly divided into three groups:control group (n=48), CINgroup (n=48) and Uremic Clearance Granule group (UCG group,n=48).To developthe CIN rat model, rats of CIN and UCG groups were injected76%MeglumineDiatrizoate Injection (10ml/kg) by rat tail vein while rats of control group were givensame amount of saline. A week before the injection, rats of UCG group were givenUremic Clearance Granule (2.5g/kg/d) by Intragastric while CIN group were givensame amount of saline. Six rats of each group were sacrificed at6h,12h,24h,48h,72h,5d,10d,15d respectively after intravenous injection, and sample of rat blood andkidney were obtained. The level of serum creatinine(Scr) and Urea nitrogen(BUN)will be measured by biochemistry detection. The renal tubular injury will be assessedby HE staining. The protein and mRNA expressions of kidney injury molecule-1(KIM-1);nuclear transcription factor-κB(NF-κB);tumor necrosis factor-α(TNF-α)in renal tissue were semiquantitatively measured with immunohistochemistry andreverse transcriptase polymerase chain reaction(RT-PCR) respectively.Results:1.Renal function:The level of Scr,BUN in control group is little change at eachtime point(P>0.05).The levels of Scr and BUN increased gradually in the CIN andUCG group after intravenous injection, and its peak is at48h, after that, the levels ofScr and BUN go down slowly. Although the trends of Scr, BUN level in UCG groupSimilar with CIN group, the Scr, BUN level in UCG group was significantly lower than that of CIN group at each time points except at10d and15d (P <0.05).2.Pathological score:No evident damage of the tubulointerstitial in control group wereseen(P>0.05). The histological examination with HE-stain revealed renal tubularinjury start at6h after injecting iodinated contrast media. Different extents of acutetubular injury with tubular brush border loss, focal structure damage,cell degenerationand necrosis and regeneration were detected, which were more severe in medulla thanthose in cortical tissue at48h. In addition, there are some inflammatory cellsinfiltration and fibrosis in the renal interstitial. The degree of renal tubular injury inUCG group is significant alleviation at each time points except at15d compared withCIN group (P<0.05).3.Immunohistochemistry and RT-PCR:There is no significantchange about the protein and mRNA levels of KIM-1, NF-κB and TNF-α in controlgroup(P>0.05).The protein and mRNA expression of KIM-1, NF-κB and TNF-α inboth CIN group and UCG group was upregulated compared to the control group.Thepeak of KIM-1in CIN group and UCG group was at24h, while the peak of TNF-αand NF-κB was at48h. The average optical density, positive rate and positive area ofKIM-1, NF-κB and TNF-α in UCG group was significantly less than the CIN group(P <0.05,).The mRNA expression of KIM-1,NF-κB and TNF-α in UCG group is alsodown-regulated compared with the CIN group (P <0.05).Conclusion:1.Uremic Clearance Granule can alleviate renal injure of rat with CIN.2.Expressions of NF-κB and TNF-α in renal tissue of CIN group rats areupregulated. Uremic Clearance Granule prevent CIN maybe by down-regulating theexpressions of NF-κB and TNF-α in renal tissue....
Keywords/Search Tags:Contrast induced nephropathy(CIN), Uremic Clearance Granule, kidneyinjury molecule-1(KIM-1), nuclear transcription factor-κB(NF-κB), tumor necrosisfactor-α(TNF-α)
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