榄香烯抑制尾加压素-Ⅱ诱导的人晶状体上皮细胞增殖的信号转导机制

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目的:探讨榄香烯(elemene,Ele)抑制尾加压素Ⅱ(Urotensin Ⅱ,U-Ⅱ)诱导的人晶状体上皮细胞(hu-man lens epithelial cell,HLEC)增殖及信号转导机制。方法:将U-Ⅱ诱导体外培养的HLEC发生增殖,并用不同浓度的Ele与其共同孵育后,用四甲基偶氮唑蓝(methyl thiazolyl tetrazolium,MTT)法检测HLEC的活性;用流式细胞术(flow cytometer,FCM)检测HLEC增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)表达;用荧光分光光度法检测HLEC内游离钙离子浓度[Ca2+]i;用放射免疫分析法检测HLEC内环化腺苷酸(cyclicadenosine monophosphate,cAMP)和环化鸟苷酸(cyclic guanosine monophosphate,cGMP)浓度。结果:U-II组HLEC活性、PCNA蛋白表达和cGMP浓度均高于对照组(P<0.001);Ele组HLEC活性、PCNA蛋白表达和cGMP浓度均比U-II组降低(P<0.001)。U-II组HLEC[Ca2+]i比对照组显著升高(P<0.001);Ele组与U-II组比较[Ca2+]i也显著升高(P<0.001)。U-II组cAMP浓度比对照组显著降低(P<0.001),Ele组cAMP浓度与U-II组比较显著升高(P<0.001)。结论:Ele可抑制U-II诱导的HLEC增殖。[Ca2+]、cAMP-PKA、cGMP-PKG是其重要的细胞信号转导机制。Ele有可能成为防治后发性白内障的有效药物。 Objective: To investigate the effects of elemene (Ele) on the proliferation and signal transduction of human lens epithelial cell (HLEC) induced by urotensin Ⅱ (U-Ⅱ). Methods: The HLEC cultured in vitro induced by U-Ⅱ was proliferated and incubated with different concentrations of Ele. After incubated with methyl thiazolyl tetrazolium (MTT), the activity of HLEC was detected by flow cytometry Flow cytometry (FCM) was used to detect the expression of proliferating cell nuclear antigen (PCNA) in HLEC. The intracellular free calcium concentration [Ca2 +] i in HLEC was detected by fluorescence spectrophotometry. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) concentrations. Results: The HLEC activity, PCNA protein expression and cGMP concentration in U-II group were higher than those in control group (P <0.001). The HLEC activity, PCNA protein expression and cGMP concentration in Ele group were lower than those in U-II group (P <0.001). The HLEC [Ca2 +] i in U-II group was significantly higher than that in control group (P <0.001), while the Ca2 + i in Ele group was significantly higher than that in U-II group (P <0.001). The concentration of cAMP in U-II group was significantly lower than that in control group (P <0.001), and the cAMP concentration in Ele group was significantly higher than that in U-II group (P <0.001). Conclusion: Ele inhibits the proliferation of HLEC induced by U-II. [Ca2 +], cAMP-PKA and cGMP-PKG are important cellular signal transduction mechanisms. Ele has the potential to become an effective drug in the prevention and treatment of post-cataract.
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