The Study of Immunological Mechanism on the Acute Renal Failure Induced by High-dose Cisplatin

Objective: Chemokines are a class of cytokines, plays an important role in the maintenance of the immune system itself stable equilibrium and function. CXC chemokine factor to its receptor CXCR1/CXCR2 combined occurrence of neutrophil-mediated inflammation, the development of the key, and the antagonist-G31P may CXCR1/CXCR2 high affinity binding CXCR1/CXCR2, thereby blocking CXC chemotactic of cytokine-mediated inflammation. Cisplatin and other platinum-induced drug is highly effective broad spectrum anticancer drugs for the treatment of solid tumors, such as ovarian, testicular germ cell tumors and one of the head and neck cancer is the most effective and the most commonly used drug, and thus widely used clinically, But at the same time it also exists a variety of toxicity, renal toxicity (acute renal failure, ARF) and gastrointestinal reactions, and cause ototoxicity, neurotoxicity, bone marrow suppression, allergic-like reactions, low blood magnesium and calcium and other side effects, including acute renal failure is the most serious complication known as cisplatin treatment. Cisplatin nephrotoxicity is cumulative and dose dependent. Although toxic, due to a good therapeutic effect, cisplatin is still one of the most commonly used chemotherapy drugs. Therefore, study cisplatin-induced ARF in the pathogenesis of a method of inhibiting cisplatin toxicity treatment methods for clinical development is very important. Recently, the role of inflammation in the ARF is increasingly being taken seriously, and gradually and neutrophil adhesion molecules, chemokines, cytokines associated. Cisplatin-induced acute renal failure, and neutrophils related inflammatory mediators and renal tissue. This article seeks to use CXCR1/CXCR2 antagonist-G31P observed intervention effect of high-dose cisplatin-induced acute renal failure, and to investigate the immunological mechanism. Methods: C57BL / 6 mice a single intraperitoneal injection of cisplatin, 15mg/kg, IP, G31P experimental group and subcutaneous injection G31P 500μg/kg positive control group was injected with the same amount of saline. Model mice were observed state conditions. Modeling, respectively 6h, 12h, 24h, 48h, 72h the eye canthus venous blood, serum urea nitrogen (BUN) and creatinine (SCr) was measured content; After the mice were killed, whichever kidneys kidney weight measurement, calculated renal coefficient; take part kidney tissue extract total mRNA of CXCR2 receptor in the RT-PCT, and agarose gel electrophoresis detection of renal tissue cytokines IL-6, IL-10.IFN.TNF of mRNA expression. Results: The positive control group and the experimental group, serum BUN and SCr levels increased. Give G31P experimental group mouse serum BUN and SCr were significantly reversed. Receptor CXCR2. Experimental mice kidney tissue cytokines IL-6, IL-10, IFN, TNF mRNA expression and the positive control group, a significant difference. Conclusion: CXCR1/CXCR2 receptor antagonist-G31P prevention of high-dose cisplatin-induced acute renal failure.