生长激素释放激素受体拮抗剂对翼状胬肉上皮细胞生长的影响及机制

目的　探讨生长激素释放激素受体（GHRH-R）拮抗剂对人翼状胬肉上皮细胞生长的影响及机制。方法　采用原发性翼状胬肉患者术中所取的翼状胬肉头部进行组织块培养，模拟翼状胬肉生长模型，根据翼状胬肉组织的透明度和血管化程度分为静止期翼状胬肉组（8例）和活动期翼状胬肉组（16例），并选取正常结膜上皮组织（6例）作为正常结膜组。此外，采用10 μmol·L^-1 GHRH-R拮抗剂MIA602作用于8例活动期翼状胬肉组的胬肉组织作为MIA602干预组。记录各组翼状胬肉上皮细胞的生长距离，并采用免疫印迹实验和免疫荧光染色检测各组GHRH-R、p-ERK1/2和Caspase-3的相对表达量。结果　与正常结膜组和静止期翼状胬肉组相比，活动期翼状胬肉组翼状胬肉上皮细胞的生长速度明显加快，并且GHRH-R和p-ERK1/2表达均显著增高，Caspase-3表达明显降低（均为P<0.05）。与活动期翼状胬肉组相比，MIA-602干预组翼状胬肉上皮细胞生长速度明显变慢，GHRH-R和p-ERK1/2蛋白表达均显著降低，Caspase-3的表达显著升高（均为P<0.05）。结论　阻断GHRH-R能够有效地抑制翼状胬肉的生长并促使翼状胬肉上皮细胞凋亡，其机制可能与降低细胞增殖能力和促进细胞凋亡有关。

Effect and mechanism of growth hormone-releasing hormone receptor antagonist on human pterygium epithelial cells

Objective　To investigate the effect and mechanism of growth hormone-releasing hormone receptor (GHRH-R) antagonist on human pterygium epithelial cells (PECs). Methods　The heads of pterygium taken from patients with primary pterygium were selected for explant culture to simulate the pterygium growth model. According to transparency and vascularization, pterygiums were divided into the quiescent group (n=8) and the active group (n=16). Besides, normal conjunctival epitheliums (n=6) were selected into the normal control group. Eight active pterygium samples were treated with 10 μmol·L^-1 GHRH-R antagonist MIA602 and included in the MIA602 intervention group. The growth distance of PECs in each group was recorded. The relative expression levels of GHRH-R, phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and cysteine protease-3 (Caspase-3) were detected by Western blot and immunofluorescence. Results　Compared with the normal control group and the quiescent group, PECs grew faster in the active group, the expression levels of GHRH-R and p-ERK1/2 were remarkably increased, while the expression level of Caspase-3 was significantly decreased (all P<0.05). Compared with the active group, PECs grew slower in the MIA602 intervention group, the expression levels of GHRH-R and p-ERK1/2 were dramatically decreased, while the expression level of Caspase-3 was significantly increased (all P<0.05). Conclusion　Blockade of GHRH-R can effectively suppress the growth of pterygiums and promote PECs apoptosis. The mechanism may be related to proliferation inhibition and apoptosis promotion.