ABSTRACT
Objective To investigate the expression of NLRP3 in different time point of HIBD neonatal rats and to search for critical time points and alleviate HIBD dysfunction.Methods 96 newborn rats of 7 days old were randomly divided into HIBD group(n=48) and Sham operation group(n=48).HIBD model was prepared by referring to Rice method.Brain tissue was taken after 6 h,24 h,72 h,7 d.Brain injury was detected by HE stain.The expression and distribution of NLRP3 and Caspase-1 were detected by immune fluorescence and Western blot,and IL-1β and IL-18 were detected by ELISA.Results HE staining and immunofluorescence showed that NLRP3 protein (HIBD group (0.63±0.07),Sham group(0.43±0.04)) was increased significantly since 6 h in HIBD group,and its downstream protein Caspase-1,IL-1β and IL-18 were successive activated.The results showed IL-1β (HIBD group(732.28± 108.42)pg/ml,Sham group(584.58± 36.35) pg/ml) was increased significantly since 6 h in HIBD group;Caspase-1 (HIBD group(0.67±0.09),Sham group(0.30±0.05)),IL-18 (HIBD group(683.84±31.83) pg/ml,Sham group(571.32±50.91) pg/ml) was increased significantly since 24 h in HIBD group(P＜0.05).Conclusion NLRP3 and its downstream inflammatory cytokines IL-1 β and IL-18 are up-regulated when HIBD occurs.The change of NLRP3protein expression in group HIBD is earlier than changes of neuron.NLRP3 signal may mediate and participate in the occurrence and development of HIBD.
ABSTRACT
OBJECTIVE:To study the bioequiavailability of sodium/calcium folinate for injections in healthy volunteers.METHODS:By a randomized crossover design,trichloracetic acid was used to precipitate the protein in serum sample.Serum concentration of folinate was determined by RP-HPLC.The pharmacokinetic parameters and relative bioavailability of sodium folinate for injection vs.calcium folinate for injection were computed and analyzed statistically.RESULTS:The pharmacokinetic parameters of single dose of sodium folinate for injection(trial formulation)vs.calcium folinate for injection(reference formulation)were as follows:tmax(0.292?0.096)h vs.(0.25?0)h;Cmax(31.973?4.337)?g?mL-1 vs.(33.332?3.312)?g?mL-1;AUC0～24(139.670?13.859)?g?h?mL-1 vs.(144.401?13.574)?g?h?mL-1;AUC0～∞(154.246?16.481)?g?h?mL-1 vs.(161.306?17.871)?g?h?mL-1;MRT0～24(6.795?0.73)h vs.(6.963?0.713)h;t1/2(7.183?1.469)vs.(7.316?2.045).The mean relative bioavailability of the sodium folinate for injection was(98.2?37.1)%.CONCLUSION:The two formulations are proved to be bioequivalent.