激活素A介导的凋亡在腰椎间盘真空变性患者中的作用

Role of activin A mediated apoptosis in patients with lumbar disc vacuum degeneration

目的探讨激活素A介导的凋亡在腰椎间盘真空变性患者中的作用。方法选取合并真空现象的腰椎间盘退变性患者作为观察组,同期住院的腰椎爆裂性骨折作为对照组,测定两组患者髓核组织中激活素A蛋白和mRNA的表达。将分离的人腰椎间盘髓核细胞随机分为3组,即对照组、激活素A组、激活素A+卵泡抑素组,继续培养48 h,检测三组细胞的增殖、凋亡和相关蛋白的表达。结果腰椎间盘真空变性患者的髓核组织中激活素A蛋白和mRNA的表达均高于对照组患者(P<0.001)。激活素A组细胞的p-Smad3蛋白表达量、细胞增殖抑制率、细胞凋亡率及Bax、Active caspase 3蛋白表达量均高于对照组(P<0.001),Bcl-2蛋白表达量低于对照组(P<0.001),而卵泡抑素则可不同程度的抑制激活素A的上述生物学效应(P<0.001)。结论激活素A在腰椎间盘真空变性患者中呈高表达,激活素A可激活Smad3信号通路,抑制髓核细胞增殖,通过线粒体凋亡途径诱导髓核细胞凋亡,卵泡抑素可拮抗激活素A的促凋亡效应,为腰椎间盘真空变性的治疗提供了新的思路。

Objective To explore the role of activin A mediated apoptosis in patients with lumbar disc vacuum degeneration. Methods The expression of activin A protein and mRNA in the nucleus pulposus of patients with lumbar disc vacuum degeneration was measured. The isolated human lumbar intervertebral disc nucleus pulposus cells were randomly divided into Control group, Activin A group and Activin A+follistatin group. The proliferation, apoptosis and expression of related proteins were detected after 48 hours of culture.Results The expression of activin A protein and mRNA in nucleus pulposus of patients with lumbar disc vacuum degeneration was higher than that of control group(both P<0.001). The expression of p-Smad3 protein, the inhibition rate of cell proliferation, apoptosis rate, the expression of Bax and Active caspase 3 protein in activin A group were higher than those in control group(all P<0.001), while the expression of Bcl-2 protein was lower than that in control group(P<0.001). Follistatin could inhibit the above biological effects of activin A to some extent(all P<0.001).Conclusion Activin A is highly expressed in patients with lumbar intervertebral disc vacuum degeneration. Activin A can activate the Smad3 signaling pathway, inhibit the proliferation of nucleus pulposus cells and induce nucleus pulposus cells apoptosis through mitochondrial apoptosis pathway. Follistatin can antagonize the pro-apoptotic effect of activin A, which provides a new idea for lumbar disc vacuum degeneration.