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Conservation Of Rosuvastatin For The Acute Kidney Injury After Coronary Artery Intervention IL-18 Receptor Expression In Renal Tubular Epithelial Cells And Its Signal Transduction In Cells

Posted on:2018-01-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:N LinFull Text:PDF
GTID:1314330566456810Subject:Doctor of Clinical Medicine
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Objective As wide use of the coronary artery intervention diagnosis and reatment,patients through the iodine contrast agent imaging and interventional treatment increased year by year,so acute kidney injury leading by iodine is attracted more and more attention.More researches are focus on CAN and inflammation of the medium is the main cause of acute kidney injury.The inflammatory response and the inflammatory cytokines are play an important role in this process.Inhibiting the inflammatory responseand,reducing inflammation cytokines maybe alleviate the contrast-induced acute kidney injury.Statins plays a decisive role in the treatment of coronary heart disease,in addition to improve blood lipid,at present,it was recognized about the function of anti-inflammatory.It,s anti-inflammatory effects to improve acute kidney injury need further research.This paper we investigated the different rosuvastatin dosage effect on protection of kidney damage caused by iodine contrast agent through research sensitive inflammatory cytokines of IL-18,?2-microglobulin,Cys C and the conventionl indicators of BUN,Scr,Ccr,GFR,discussing different doses of rosuvastatin whether there is difference of renal protective effect,in order to choose the right dose to alleviate acute kidney injury.Acute kidney injury is mainly associated with inflammatory reaction,there have two damage forms about the acute kidney injury:Directly injury and Indirectly injury.It is found that cytokine plays an important role in the the acute kidney injury.IL-18 can be found many kinds of renal diseases closely related to IL-18.There is no further research results about the role of IL-18 in kidney damage mechanism.This paper preliminarily studies IL-18 influence on renal tubular epithelial cells,explore its mechanism conduction in the cell.it will provide the theoretical support about contrast media-induced acute kidney injury research in the aspect of molecular biology,inorder to provide theoretical support for the study of better prevention and treatment of acute kidney injury.Methods Choose a total of 896 patients who were in hospital of department of cardiology with diagnosis and treatment through the coronary artery intervention.The selected patients were randomly divided into the control group(270 cases),the conventional dose of rosuvastatin treatment group(10mg/d 295 cases)and the high dose of rosuvastatin treatment group(20mg/d 331 case).Observing the three groups of patients with preoperative,postoperative 24 h,6 weeks after operation if there was the difference of IL-18,?2-microglobulin,Cys C,BUN,Scr,Ccr,GFR to explore if there is difference for rental protection with different rosuvastatin doses.With the help of proximal renal tubular epithelial cell line(HK2),using RT-PCR method detection on HK2 IL-18 receptor expression.By western blot method to observe the different concentration of IL-18 intervention HK2 cells after 12 h,24h,48 h HK2 cells damage markers RNATES changes,explore its mechanism conduction in the cell.Results 1.Based on the related indicators during postoperative 24 hours,compared with preoperative,through the pairwise comparison of three groups,we found that the degree of inflammatory cytokines IL-18,?2-microglobulin,Cys C were all elevated,the rosuvastatin treatment group was inferior to the control group(P<0.05).Ccr,GFR were all bringing down,the rosuvastatin treatment group was inferior to the control group(P<0.05),there have no statistical difference in two rosuvastatin treatment group(P<0.05),there have no obvious difference about three groups,there have no statistical difference(P>0.05);2.We were also determined the index of three groups after six weeks,IL-18,?2-microglobulin,Cys C were all droped,Ccr,GFR were all elevated,IL-18,?2-microglobulin,Cys C Ccr,GFR were all to return to baseline levels of preoperative,there have no statistical difference(P>0.05).3.We use agarose electrophoresis nucleic acid and protein imprinting analysis method to detect normal culture HK2 receptors IL-18R;It showed that IL-18 stimulate expression of RANTES time and concentration dependently.4.Experimental observation that IL-18 effect of the JAK-STAT6 signaling pathways,leflunomide inhibits this signaling pathway start.Conclusion 1.No matter how much dose of the conventional dose rosuvastatin treatment or the high dose rosuvastatin treatment were given preoperative can effectively inhibit the production of inflammatory cytokines in 24 hours by iodine contrast agent.2.For a long time observation,we can not found there have more advantage of the high dose rosuvastatin to inhabit inflammatory cytokines.3.This study found that human proximal renal tubular epithelial cells express IL-18 R,it lay a strong foundation to disscuss thecontrast-induced nephropathy pathogenesis.4.This study also found that IL-18 damage to the human proximal tubular epithelial cells by the the corresponding receptors,JAK-STAT6 signal pathway activation is closely related,it will provide the theoretical support about contrast media-induced acute kidney injury research in the aspect of molecular biology.
Keywords/Search Tags:Rosuvastatin, Contrast media-induced acute kidney injury, Interleukin-18, Human proximal tubular epithelial cells, Mechanism of action
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