促性腺激素释放激素激动剂对子宫腺肌病病灶及子宫内膜Ki-67、VEGF、NGF表达及神经纤维分布的影响

GnRHa inhibits expression of Ki-67,VEGF,NGF and reduces nerve fiber density of endometrium in patients with adenomyosis

目的探讨促性腺激素释放激素激动剂(GnRHa)对子宫腺肌病患者子宫腺肌病病灶及子宫内膜细胞增殖、血管增殖、神经生长因子及神经纤维密度的影响。方法选取2014年1月至2020年6月绍兴市人民医院收治的因子宫腺肌病行经腹或腹腔镜下子宫全切术的患者68例,其中36例患者选择术前GnRHa预处理作为GnRHa治疗组,另外32例患者选择直接手术治疗作为对照组。检测比较两组患者子宫腺肌病病灶及子宫内膜增殖细胞相关核抗原-67(Ki-67)、血管内皮生长因子(VEGF)、神经生长因子(NGF)、蛋白基因产物-9.5(PGP-9.5)的表达情况。结果GnRHa治疗组和对照组患者子宫腺肌病病灶组织Ki-67阳性细胞比例分别为(9.56±3.48)%和(44.53±10.02)%,差异有统计学意义(P<0.05);两组子宫内膜组织Ki-67阳性细胞比例分别为(7.56±2.27)%和(43.66±9.87)%,差异有统计学意义(P<0.05)。GnRHa治疗组和对照组患者子宫腺肌病病灶组织VEGF阳性细胞比例分别为(6.06±1.71)%和(10.09±2.43)%,差异有统计学意义(P<0.05);两组子宫内膜组织VEGF阳性细胞比例分别为(6.86±2.28)%和(7.69±2.84)%,差异无统计学意义(P>0.05)。GnRHa治疗组和对照组患者子宫腺肌病病灶组织NGF免疫反应性(IR)评分比例分别为3.92±1.20和6.84±2.68,差异有统计学意义(P<0.05);在子宫内膜部位,两组IR评分比例分别为2.78±1.57和5.66±2.81,差异有统计学意义(P<0.05)。GnRHa治疗组和对照组患者子宫腺肌病病灶组织PGP-9.5阳性神经纤维密度分别为1(1,2)和3(2,4),差异有统计学意义(P<0.05);两组子宫内膜组织PGP-9.5阳性神经纤维密度分别为1(1,2)和2(1,3),差异有统计学意义(P<0.05)。结论经GnRHa治疗可显著减少子宫腺肌病病灶及子宫内膜的细胞增殖及神经纤维分布,可显著减少子宫腺肌病病灶血管增殖,并对子宫内膜的血管增殖有一定抑制作用。

Objective To assess the effects of gonadotropin-releasing hormone agonist(GnRHa)on cell proliferation,vascular proliferation,nerve growth factor and nerve fiber density in endometrium of patients with adenomyosis.Methods Sixty-eight patients with adenomyosis undergoing hysterectomies were enrolled in this study,of whom 36 had GnRHa treatment prior to hysterectomy(GnRHa group),and 32 did not have preoperative GnRHa treatment(control group).Adenomyosis tissue samples from these patients were obtained and the tissue expression of Ki-67,VEGF,NGF and PGP-9.5 was detected with immunohistochemistry.Results The proportion of Ki-67 positive cells in adenomyosis lesions of GnRHa group and control group was(9.56±3.48)%and(44.53±10.02)%,respectively,and the difference was statistically significant(P<0.05).The proportion of Ki-67 positive cells in the endometrial tissues of the two groups was(7.56±2.27)%and(43.66±9.87)%,respectively,and the difference was statistically significant(P<0.05).The proportion of VEGF positive cells in adenomyosis lesions in Gn-RHa group and control group was(6.06±1.71)%and(10.09±2.43)%,respectively,and the difference was statistically signifi-cant(P<0.05).The proportion of positive cells of VEGF in endometrial tissues was(6.86±2.28)%and(7.69±2.84)%,respec-tively,and there was no statistical significance between the two groups(P>0.05).IR score of NGF expression in GnRHa group and control group was 3.92±1.20 and 6.84±2.68,respectively,and the difference was statistically significant(P<0.05).In the endometrial area,the IR score between the two groups was 2.78±1.57 and 5.66±2.81,respectively,and the difference was statistically significant(P<0.05).The density of PGP-9.5 positive nerve fibers in adenomyosis lesions of GnRHa group and control group was 1(1,2)and 3(2,4),respectively,and the difference was statistically significant(P<0.05).The density of PGP-9.5-positive nerve fibers in endometrial tissues of the two groups was 1(1,2)and 2(1,3),respectively,and the differ-ence was statistically significant(P<0.05).Conclusion GnRHa treatment can significantly reduce the cell proliferation and nerve fiber distribution in adenomyosis lesion and endometrium,and can significantly reduce the vascular proliferation in ade-nomyosis lesion.