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目的探讨17β-雌二醇(E2)和E2受体拮抗剂对Ⅰ型神经纤维瘤病(NF1)神经纤维瘤的形成和发展的影响。方法3H-TdR掺入法研究E2对施万细胞增殖能力的影响;免疫印迹(Western-blot)方法检测E2及E2受体拮抗剂Tamoxifen对NF1患者神经纤维瘤中施万细胞NF1蛋白和hTERT蛋白表达的影响。结果随着E2孵育浓度和时间的增加,CPMA值有逐渐增加的趋势,其中10-7mol/L和10-6mol/L浓度作用24(分别为224.33±25.59和242.17±21.98)和48h(分别为234.83±28.15和257.83±28.86),CPMA值增高与对照组(154.33±17.89)相比差异有统计学意义,相同E2浓度孵育24和48h相比,CPMA值的差异没有统计学意义;E2处理组与对照组比较,E2+E2受体拮抗剂Tamoxifen处理组与E2处理组比较,NF1蛋白的表达差异皆无统计学意义;E2受体拮抗剂Tamoxifen处理组与对照组比较,NF1蛋白的表达差异无统计学意义;E2处理组与对照组比较,hTERT蛋白表达增高约3.31倍,差异有统计学意义;E2+E2受体拮抗剂Tamoxifen处理组与E2处理组相比,hTERT蛋白表达约降低39%,差异有统计学意义;E2受体拮抗剂Tamoxifen处理组与对照组相比,hTERT蛋白的表达差异无统计学意义。结论E2能够促进NF1神经纤维瘤中施万细胞的增殖;E2对NF1中神经纤维瘤形成的促进作用是通过提高hTERT蛋白表达,进而增加端粒酶活性促进细胞增殖这一通路实现的,而非上调NF1蛋白表达。E2的这一作用可以被E2受体拮抗剂Tamoxifen抑制。
Objective To investigate the effects of 17β-estradiol (E2) and E2 receptor antagonist on the formation and development of type 1 neurofibromatosis (NF1) neurofibromas. Methods 3H-TdR incorporation was used to investigate the effect of E2 on the proliferation of Schwann cells. Western blotting was used to detect the effect of E2 and E2 receptor antagonist Tamoxifen on NF1 and hTERT protein expression in Schwann cells The impact of expression. Results With the increase of concentration and time of E2 incubation, the CPMA value tended to increase gradually. The concentrations of 10-7mol / L and 10-6mol / L of 24 (224.33 ± 25.59 and 242.17 ± 21.98, respectively) and 48h 234.83 ± 28.15 and 257.83 ± 28.86, respectively. There was significant difference between the CPMA value and the control group (154.33 ± 17.89). There was no significant difference in CPMA value between 24 and 48 hours after E2 incubation Compared with the control group, there was no significant difference in the expression of NF1 between the E2 + E2 receptor antagonist Tamoxifen and the E2 treatment groups; the difference was not found between the NF1 protein expression of the E2 receptor antagonist Tamoxifen group and the control group There was no significant difference between the E2 treatment group and the control group, hTERT protein expression increased about 3.31-fold, the difference was statistically significant; E2 + E2 receptor antagonist Tamoxifen treatment group compared with the E2 treatment group, hTERT protein expression decreased by about 39 %, The difference was statistically significant. There was no significant difference in the expression of hTERT protein between the Tamoxifen-treated group and the control group. Conclusion E2 can promote the proliferation of Schwann cells in NF1 neurofibromatosis. The promoting effect of E2 on the formation of neurofibromas in NF1 is achieved by increasing the expression of hTERT protein and increasing the telomerase activity and promoting the proliferation of cells Upregulate NFl protein expression. This effect of E2 can be inhibited by the E2 receptor antagonist Tamoxifen.