| Part1: The protective effect of lipoic acid on paraquat-induced renalinjury in ratsObjective: To build PQ-induced renal injury model in rats, to observe the changes ofbehavior, body weight and renal function, and to take pathological observation of kidneytissue.Methods:120healthy male Sprague Dawley (SD) rats were randomly divided into fourgroups: normal control group (NC group),model group (PQ group) and treatment group(LA group),LA group was further divided into LA1and LA2group, with each group had30rats. According to different observation points (6h,12h,24h,48h,72h), all groups wererespectively divided into5subgroups, with each group had6rats. PQ poisoning model wasreproduced by intraperitoneal injecting PQ (25mg/kg), NC group received same doses ofsaline. LA group were given lipoic acid by tail vein injection (54.18mg/kg and100mg/kg)after30min. Then each subgroups were given lipoic acid as above at24h,48h and72h, PQgroup also received same doses of saline. In the corresponding time points, blood from theabdominal aorta and nephridial tissue were taken after being measured body weighteveryday. Observe changes of behavior, monitor renal function, morphology and pathologyof renal tissue. Results:①pathological observation: NC group presented a normal kidney structure, thepathological damage of PQ group and LA group was more serious than NC group, whilethe pathological damage of LA group was lighter than PQ group, especially LA2group。②The body weight: the weight reduction in LA1group at24h,48h and72h was significantlyless than PQ group（P＜0.01,P＜0.05and P＜0.01)。Compared with PQ group，LA2group alsohad significant statistical differences at24h,48h and72h（all P＜0.01）。The body weightbetween LA1and LA2group at72h had significant difference（P＜0.01）。③Renal function:There were no significant differences in Cr among groups at different time points（P＞0.05）。The increase of BUN in LA1group at12h,24h and72h was significantly less than PQgroup（P＜0.01,P＜0.01and P＜0.05)。Compared with PQ group，LA2group also hadsignificant statistical differences at12h,24h,48h and72h（all P＜0.01）。BUN between LA1and LA2group at12h,24h had significant differences（P＜0.01, P＜0.01）。Conclusions: We successfully built PQ-induced renal injury model in rats byintraperitoneal injection of PQ（25mg/kg），and we observed that the body weight wasgradually decline, BUN continued to rise, pathological damage were severe。 Afteradministrated lipoic acid, the above changes were significantly reduced, especially LA100mg/kg，its protective effect is remarkable。 Part2: lipoic acid induced the expression of Nrf2and HO-1inparaquat-related renal injury in ratsObjective: Through observing the effect of lipoic acid on paraquat-related renal tissueoxidative stress indexes of SOD and MDA, and the expression of nuclear transcriptionfactor Nrf2and its downstream HO-1, to discuss whether anti-oxidative stress effect oflipoic acid is related to the activation of Nrf2/HO-1signal pathway, and to provide a new theoretical basis for the treatment of lipoic acid.Methods: The procedure was the same as above, renal tissue specimens were used to detectthe activity of SOD and MDA by ELISA, detect the expression of Nrf2and HO-1byRT-PCR.Results:①enzyme activity: the activity of MDA in PQ group was the highest at48h, therewas no significantly decreased at72h. MDA between LA1and LA2group at all differenttime points were higher than NC group（P＜0.05）,but lower than PQ group（P＜0.05）,LA2group was lower than LA1group at24h,48,72h（P＜0.05）; the activity of SOD between PQand LA group were significantly lower than NC group（P＜0.01）, while LA1and LA2groupwere significantly higher than PQ group（P＜0.01）,SOD between LA1and LA2group at72h has statistics differences（P＜0.05）。②Nrf2and HO-1mRNAexpression:Nrf2mRNA in PQ group was the highest at12h, thengradually decreased. LA1group at24h,48h,72h were significantly higher than PQ group（all P＜0.01）, while LA2group at12h,24h,48h,72h were significantly higher than PQgroup（all P＜0.01）, Nrf2mRNA in LA2group at12h,24h,48h were significantly higherthan PQ group（all P＜0.01）; HO-1mRNA in PQ group was the highest at6h, thengradually decreased. LA1group at12h,24h,48h,72h were significantly higher than PQgroup（all P＜0.01）, while LA2group at all time points were significantly higher than PQgroup（all P＜0.01）,there was significant statistical difference at12h,24h,48h,72h betweenLA1and LA2group（all P＜0.01）.Conclusions: There was oxidative stress injury in renal tissue after paraquat poisoning inrats. The activity of MDA increased gradually and SOD decreased on the contrary. Afteradministrate lipoic acid, we observed obvious protective effect, and its protection wasassociated positively with lipoic acid dose. We considered that the protective effects oflipoic acid on paraquat poisoning renal injury may be related to Nrf2/HO-1signal pathwayactivation. |
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