Effects Of Methamphetamine On Renal Injury In Rats

2015 China Drug Situation Report shows:China cracked 145,900 drug-related criminal cases,drugs seized a total of 68.96 tons,including 25.9 tons of drugs like methamphetamine,ketamine 11.2 tons,9.3 tons of heroin,4 tons of marijuana.The total number of registered drug users in 2,950,000,including the abuse of new drugs staff of 1,459,000,accounting for the number of drug users in 49.4%,for the first time in more than 49.3%of the proportion of heroin abuse groups,and in the new drug abusers,the abuse of methamphetamine staff of 1 million 190 thousand,accounting for 81.6%of the number of new drug drug and drug abuse that China has undergone profound changes in the structure;amphetamine type stimulants to methamphetamine(AST)as the main body of the abuse and dependence is spreading rapidly in the world and China,much to replace the traditional drugs such as heroin and cocaine trend,China is facing the threat of heroin after methamphetamine abuse.Yunnan province is located in the southwest of China.Its border area is beautiful,the climate is pleasant,the nationality is numerous,and the frontier trade is prosperous.It is a historical and cultural scenic spot since ancient times.Since the reform and opening up,from the "Golden Triangle" area by the amount of drug transport in Yunnan and the border area is larger and more frequent drug trafficking,serious harm to the normal life of the people and the border of the normal economic order,but also makes our country from the past drug transit gradually become victim of manufacturing,production,sale and consumption a "one-long".At present,due to the abuse of new drugs,especially methamphetamine,there are a lot of people,so this study will discuss the damage of methamphetamine to kidney.Objectives:To investigate the abuse of new drug methamphetamine(MA)to investigate the mechanism of renal injury,this study is divided into two parts,the first part is the research of methamphetamine damage in human renal proximal tubular epithelial cells(HK-2,cells),cell toxicity test and cell apoptosis by MTS method,and acute injury markers neutrophil gelatinase associated lipocalin(Ngal),renal damage factor(Kim-1)expression and secretion,and the renal toxicity of methamphetamine injury in this paper.The second part is to establish the kidney injury model of methamphetamine in rats,and to study the mechanism of methamphetamine damage to kidney in rats.Methods:To observe the damage of methamphetamine on epithelial cells of proximal convoluted tubule of human kidney.Experiment group:normal control group(only with medium),control group with different concentrations of 0.75mmol/L,lmmol/L,1.5mmol/L,2mmol/L,3mmol/L,4mmol/L,6mmol/L,8mmol/L,12mmol/L,16mmol/L of methamphetamine in vitro cultured human renal proximal tubular epithelial cells,the effect of MTS was observed on HK-2 methamphetamine,flow cytometry to observe the changes of cell cycle and apoptosis,ELISA method was used to detect the secretion of Ngal and Kim-1 culture supernatant.Through the establishment of acute,subacute and chronic rat models of methamphetamine,the renal tissues of rats were sectioned,stained with HE and scanned by electron microscopy.Results:(1)the effect of methamphetamine on human renal tubular epithelial cells 24h,microscopic observation of cell morphology,and the survival rate of cells by MTS method.In the 0.75mmol～16mmol/L concentration range,the survival rate of HK-2 cells decreased as methamphetamine concentration increased.The proliferation test showed that,compared with the control group at the same time,when the concentration reached 6mmol/L～16mmol/L,the effect of methamphetamine on HK-2 cell 24h was statistically significant(P<0.05).(2)the apoptosis of HK-2 cells induced by methamphetamine:group 0.75mmol/L:20.51%;1mmol/L:24%;1.5mmol/L:31.96%;2mmol/L:30.15%;3mmol/L:31.8%;4mmol/L:26.9%;6mmol/L:99%;8mmol/L:98%;12mmol/L:99.16%;16mmol/L group:99.8%.(3)NGAL results:compared with the control group,8mmol/L group and 12h group increased the secretion of NGAL in renal tubular epithelial cells as the action time prolonged.The secretion of NGAL gradually decreased after 12h in the renal tubular epithelial cells.(4)KIM-1 results:compared with the control group,8mmol/L group and 48h group increased the secretion of KIM-1 in renal tubular epithelial cells as the action time prolonged.Conclusion(s):(1)methamphetamine inhibited the proliferation of HK-2 cells.When the concentration was 6mmol/L-16mmol/L,the inhibitory effect of methamphetamine on HK-2 cells was stronger than that of 24h.(2)the apoptosis of HK-2 cells induced by methamphetamine.(3)in 12h,the amount of NGAL secreted by renal tubular epithelial cells increased with the prolongation of action time.The secretion of NGAL gradually decreased after 12h in the renal tubular epithelial cells.(4)the secretion of KIM-1 increased in renal tubular epithelial cells as the action time prolonged.(5)MA has obvious toxic effect on kidney.