ABSTRACT
Objective:To study the effect of sinomenine hydrochloride on dextran sulfate sodium(DSS) induced experimental colitis in mice. Methods:The colitis model of BALB/c mice was established with DSS. The mice were randomly divided into six groups (n = 6):the normal control group and the model group(giving normal saline,0.2 ml),salicylazosulfapyridine treatment group (100 mg·kg-1) and sinomenine treatment groups (30,90,270 mg·kg-1). After continuous administration for 10 d,the disease activity index (DAI) and the tissue damage index in each group were evaluated. The mouse colons of TLR4 and Myd88 were detected using Western-blotting, and the expression of NF-κB in the colon tissues was detected using immunohistochemical method. Results:The DAI and the tissue damage index, and the expressions of TLR4, Myd88 and NF-κB in the colon tissues were significantly higher in the model group than those in the normal group (P < 0.01). Sulfasalazine treatment group and sinomenine at low,medium and high dose groups could reduce the DAI and the tissue damage score,and the expressions of TLR4, Myd88 and NF-κB in the colon tissues (P < 0.01) in a concentration-dependent manner. There was no significant difference between salicylazosulfapyridine treatment group and sinomenine at medium/high dose groups. Conclusion:Sinomenine reduces the expression of TLR4,Myd88 and NF-κB in mice with experimental colitis by regulating the TLR4/NF-k B signaling pathway to play a therapeutic role.
ABSTRACT
AIM: To explore the immunity modulation function of aqueous of Forsythia suspense (AFS) and its possible mechanisms. METHODS: Rats of burned model group were burned with vapor under 3mpa pressure and 108℃ temperature for 8 seconds to achieve deep partialthickness bum, to make a thirty percent total body surface area (TBSA)bum. The experiment were divided into five groups: Control group: without any treatment; 8 PBH group: 8 h after burn; the rats of AFS1 guoup, AFS2 group and AFS3 group of them were given AFS 5 g/kg, 2.5 g/kg, 1.25 g/kg once a day by Po. pathway for seven days before burns, respectively. Rats were sacrificed before and 8h after burn, The percentage of Treg cells in CD4~+ T cells was detected by flow cytometry(FCM) ; the expression of Foxp3 mRNA on splenocytes were measured by RT-PCR, and the protein of Foxp3 activity was evaluated by immunohistochemistry staining. RESULTS: Compared with Control group, the expression of Foxp3mRNA and protein on the splenocytes were upregulated markedly(P <0.01), and the percentage of Treg were significantly increased (P < 0.01) in the 8PBH group. AFS1, AFS2 and AFS3 significantly attenuated these increases (P < 0.01), which was dose-dependent. CONCLUSION: AFS has immunity modulation function and mechanism of it is corrected with Foxp3 mRNA on splenocytes.
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Aim To study the pharmacokinetics and bioequivalence of nimesulide dispersible tablet and its normal tablet. Methods 20 healthy volunteers were treated with a single oral dose of domestic nimesulide dispersible tablet or normal tablet (control) in a randomized crossover study and the plasma drug concentration was determined by HPLC. Results The plasma concentration time curve was fitted to the one compartment model. The pharmacokinetic parameters obtained were: c max ( 3.91 ? 0.74) ?g ?ml -1 , t (1/2)? ( 3.40 ? 0.78) h , t max ( 3.15 ? 0.67) h , AUC 0～24 ( 31.92 ? 6.36) ?g ?ml?h -1 , there was no significant difference between the active and control groups. The relative bioavailability obtained was ( 96.43 ? 8.41 ) %. Conclusion The pharmacokinetic profile for the 2 tablets was similar so it may be concluded that they are bioequivalent.
ABSTRACT
Objective:To investigate a potential role of Toll-like receptor 4(TLR4) ,a pathogen pattern recognition receptor, in the early phase of severely burned rats. Methods: Rats burn model(30% of total body surface area[TBSA],Ⅲgrade) were established with vapor at 108 C for 8 seconds. Rats were sacrificed before and 2,5,12,24,48 and 72 h after burning, and the spleen specimens and peripheral blood samples were harvested. TLR4 mRNA and TNF-?mRNA expression in splenocyte was measured by reverse-transcription PCR(RT-PCR); the expression of TLR4 protein were measured by Western bloting; the endothelial toxicity concentration in plasma was detected by limulus lysate test. Results: It was found that the expression of TLR4 mRNA.TNF-?mRNA,TLR4 protein,and the level of ET were significantly increased in burned group compared with normal control group. The expression of TLR4 mRNA and protein peaked at 8 h after burning, the expession of TNF-?mRNA peaked at 12 h.and the level of ET peaked at 8 h after burnings the peak values of them were (3. 66?0. 51),(2. 27?0. 19), (1.65?0. 23),and (11. 68?2. 63) Eu/ml, respectively, all significantly higher than those of the control group(P