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OBJECTIVE：To stu dy the mechanism of improvement effects of Gastrodin injection on methamphetamine induced neurotoxic damage in rats via nNOS pathway. METHODS ：SD rats were randomly divided into control group ，methamphetamine group，regular-dose of gastrodin group ，double-dose of gastrodin group ，negative control （NC）adenovirus group ，NC adenovirus+ methamphetamine group ，NC adenovirus+gastrodin group and nNOS adenovirus+gastrodin group ，with 10 rats in each group. Control group was given normal saline intraperitoneally ，twice a day. Methamphetamine group was given methamphetamine intraperitoneally（7.5 mg/kg），twice a day. Regular-dose and double-dose of gastrodin groups were respectively given different doses of Gastrodin injection （10，20 mg/kg）intraperitoneally 30 min earlier ，once a day ，and then given methamphetamine intraperitoneally by the same way as methamphetamine group. NC adenovirus group was given NC adenovirus （4.8×107 PFU）3 μL once in the striatum and normal saline intraperitoneally ，twice a day. NC adenovirus+methamphetamine group was given NC adenovirus by the same way and methamphetamine （7.5 mg/kg）intraperitoneally，twice a day. NC adenovirus+gastrodin group was given NC adenovirus+methamphetamine by the same way ，meanwhile given Gastrodin injection intraperitoneally （20 mg/kg）30 min before methamphetamine ，once a day. nNOS adenovirus+gastrodin group was given nNOS adenovirus and methamphetamine by the same way ，meanwhile given Gastrodin injection intraperitoneally （20 mg/kg）30 min before methamphetamine ，once a day. Each group was given relevant medicine intraperitoneally 1 mL/100 g，for consecutive 3 days. The stereotyped behavior of rats were observed and scored ；the apoptotic rate ，the protein expression of apoptotic factors （Bcl-2，Bax，Cleaved caspase- 3），the levels of oxidative stress factors （MDA，SOD，GPx） and NO ，the protein expression of nNOS were detected. RESULTS ： Compared with control group ，stereotyped behavior score ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase-3 and nNOS ，the levels of MDA and NO were increased significantly in methamphetamine group ；while the protein expression of Bcl- 2 and the levels of SOD and GPx were decreased significantly （P＜0.05 or P＜0.01）. Compared with methamphetamine group ，stereotyped behavior score ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase- 3 and nNOS ，the levels of MDA and NO were decreased significantly in regular-dose and double-dose of gastrodin groups ；while the protein expression of Bcl- 2，the levels of SOD and GPx were increased significantly ，and most above indexes in double-dose of gastradin group were better than regular-dose of gastrodin group （P＜0.05 or P＜0.01）. Compared with NC adenovirus group ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase- 3 and nNOS ，the levels of MDA and NO were increased significantly in NC adenovirus+methamphetamine group ；while the protein expression of Bcl- 2，the levels of SOD and GPx were decreased significantly （P＜0.01）. Compared with NC adenovirus+methamphetamine group ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase- 3 and nNOS ，the levels of MDA and NO were decreased significantly in NC adenovirus+ gastrodin group ；while the protein expression of Bcl- 2，the levels of SOD and GPx were increased significantly （P＜0.01）. Compared with NC adenovirus+gastrodin group ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase- 3 and nNOS，the levels of MDA and NO were increased significantly in nNOS adenovirus+gastrodin group ；while the protein expression of Bcl- 2，the levels of SOD and GPx were decreased significantly （P＜0.01）. CONCLUSIONS ：Gastrodin injection can protect rats against neurotoxic damage induced by methamphetamine ，and the effect is related to the inhibition of nNOS-mediated apoptosis and oxidative stress.
ABSTRACT
AIM:To study the expression of signal transduction molecules in the striatum G protein protein 4 (RGS4) and dopamine D2 receptor (D2) in conditioned place preference (CPP) rats treated with methamphetamine (meth).METHODS:METH dependence CPP model was established (1 week and 2 weeks of METH dependence groups),The protein expression of RGS4 and D2,inhibitory G protein alpha-subunit (Gαi),mitogenactivated protein kinase (MAPK) in striatum were determined by Western blotting (WB).The changes of cyclic adenosine monophosphate (cAMP) content in striatum of rats were determined by enzyme linked immunosorbent assay (ELISA).RESULTS:Compared with saline control group,the average time of rats in the methamphetamine-paired chamber for two groups was increased (P ＜ 0.05).Compared with saline control group,RGS4 protein expressions in the two METH dependent groups were reduced (P ＜0.01);compared with 1 week of METH dependence group,that of 2 weeks group was reduced significantly(P ＜ 0.05).D2,Gαi,MAPK protein and cAMP expressions in the two METH dependent groups were increased (P ＜ 0.01);compared with 1 week of METH dependence group,those of 2 weeks were increased significantly (P ＜ 0.05).CONCLUSION:RGS4 and D2 receptor signaling pathways in striatum have changed in METH dependent rats,RGS4 may be involved in the regulation of METH-dependent D2 receptor signaling pathway in METH dependent rats.
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Objective To investigate influencing factors of disability after craniocerbral injury caused by road traffic accident.Methods We collected 486 cases with craniocerebral injury caused by traffic accident,and conducted analysis.Factors related to disability were found by univariate analysis,and multivariate logistic regression analysis was conducted to filter the most important factors.Results Degrees of brain injury,drunk driving,age and types of accident were the major influencing factors.Drunk driving and age were positively related with disability grade while the degree of brain injury and type of accident were negatively related.Concuusiorn It is helpful to reduce disability and the burden on society by taking intervening measures on the related factors of disability after brain injury in road traffic accident.
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Nerve growth factor (nerve growth factor, NGF) is the earliest discovered growth factor in neurotrophic factors,it has a very important role in maintaining the survival, growth, differentiation,repair and regeneration after injury of neurons. In this paper,research progress in recent years on NGF are reviewed.