The Study Of Immunological Mechanism On The Acute Renal Failure Induced By High-dose Cisplatin

Objective:Chemokines are a class of cytokines, play a very important role in maintaining balance, stability and function of the immune system. ELR+CXC chemokines, as a class of CXC chemokines, their important role in the process of development of neutrophils inflammation is welknown, and our ELR+CXC chemokine receptor antagonists G31P can be combined with its high affinity receptor CXCR1/CXCR2, thereby block ELR+CXC chemokines role.Cisplatin and other platinum drugs are very important chemotheraputic drugs, are effective broad-spectrum anticancer drugs for the treatment of solid tumors such as ovarian, head, neck, testicular germ cell tumors and so on the most effective and the commonly used drugs , they have been widely used in clinical, but the problem of their side effects is also present, for example, renal toxicity and gastrointestinal tract reactions and also cause ear toxicity, neurotoxicity, bone marrow suppression, allergy-like reactions, low blood magnesium and calcium and other side effects.ARF(acute renal failure) is a well-known complication of cisplatin therapy . Cisplatin nephrotoxicity is cumulative and dose dependent. Although poisonous, but because of good treatment, cisplatin is still one of the most commonly used chemotherapy drugs. Therefore, the study of ARF induced by cisplatin in clinical development for the pathogenesis of cisplatin toxicity for suppressing treatment is very important.Recently, the role of inflammation in ARF is getting more and more attention, and also the association of neutrophils, adhesion molecules, chemokines and other cytokines . Cisplatin-induced acute renal failure, is related to the proinflammatory mediators and neutrophils among renal tissues. This article mainly aims to observe CXCR1/CXCR2 receptor antagonist-G31P for the prevention and treatment of high-dose cisplatin-induced acute renal failure, and to explore its mechanism.Methods:C57BL/6 mouse were given a single dose of intraperitoneal cisplatin,15mg/kg, IP, and the subcutaneous injection of G31P at the same time in the back in a dose of 500μg/kg. After modeling the activity and health of mice was observed. And also eye canthus vein blood was aspirated to measure the serum urea nitrogen (BUN) and creatinine (SCr) levels in 6h, 12h,24h,48h,72h respectively after the modeling; after the mice were killed, both kidneys were taken to measure the weight and calculate the renal factor. A portion of the total kidney was taken to extract renal mRNA, further do RT-PCT, and agarose gel electrophoresis receptors in renal tissue CXCR2, mRNA expression of cytokines IL-6, IL-10, IFN, TNF.Results:Positive control group and experimental group mice increased serum BUN and SCre levels. And the experimental mice serum BUN and SCr were significantly reversed prior to G31P. The CXCR2 receptor from the Renal tissue of experimental mice and the mRNA expression of cytokines IL-6, IL-10, IFN, TNF was significantly different from that of positive control group.Conclusion:CXCR1/CXCR2 receptor antagonist-G31P can prevent the occurrence of high-dose cisplatin-induced acute renal failure.