摘要
目的研究5,7,3'-三乙酰橙皮素(5,7,3'-triacetylhesperetin,TAHP)对佐剂性关节炎大鼠成纤维样滑膜细胞(FLS)Jak2/Stat3信号通路及凋亡相关蛋白的影响。方法用弗氏完全佐剂诱导大鼠AA模型;MTT法检测FLS的增殖反应;Hoechst 33258染色法检测FLS的凋亡;RT-PCR法检测FLS中Jak2、Stat3、Bcl-2、Bax及Caspase-3的基因表达;Western blot法检测FLS中p-Stat3及Caspase-3的蛋白表达情况。结果 TAHP呈剂量和时间依赖性抑制FLS的增殖(P<0.05);Hoechst 33258染色结果提示TAHP可以明显地促进FLS的凋亡;同时TAHP(50,250μmol·L-1)可以明显降低Jak2、Stat3及Bcl-2表达,而上调Bax及Caspase-3表达。Western blot结果显示,TAHP可降低p-Stat3的表达、上调Caspase-3表达。结论 TAHP可以抑制FLS增殖,其作用机制可能与抑制FLS Jak2/Stat3信号通路、促进Bax及Caspase-3表达、抑制Bcl-2的表达有关。
Aim To investigate the effect of 5, 7, 3＇- triacety! hesperetin （TAHP） on Jak2/Stat3 signalling pathway and related apoptosis proteins of fibroblast-like synoviocytes （FLS） with adjuvant-induced arthritis in rats. Methods Freund＇ s complete adjuvant was used to induce AA in rats. FLS proliferation response was e- valuated with MIT assay. The apoptosis of FLS was detected by Hoeehst 33258 staining. The expressions of Jak2, Stat3, Bcl-2 ,Bax and Caspase-3 mRNA in FLS were detected by RT-PCR. The protein expressions of p-Stat3 and Caspase-3 were observed by Western blot. Results The proliferation of FLS was inhibited by TAHP in a dose-and-time dependent manner. Hoechst 33258 staining indicated that TAHP could obviously in- crease the AA FLS apoptosis. The results of RT-PCR showed that TAHP（50, 250μmol·L^-1） could reduce the expressions of Jak2, Stat3 and Bcl-2 （ P 〈 0. 05 ） but up-regulate the expressions of Bax and Caspase-3. The results of Western blot showed that TAHP （50, 250 μmol·L^-1 ） could reduce the expression of p-Stat3 and up-regulate the expression of Caspase-3. Conclusions TA/-/P can inhibit the proliferation of FLS. The mechanism might be associated with inhibiting Jak2/ Star3 signalling pathway, promoting the expressions of B/ix and Caspase-3, and decreasing the expression of Bcl-2.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2012年第8期1063-1068,共6页
Chinese Pharmacological Bulletin
基金
国家重大基础研究发展计划前期(973计划前期)研究专项(No 2002CCC02900)
