Research question

Angiotensin-converting enzyme inhibition results in a significant reduction in plasma concentrations of plasminogen activator inhibitor-1 (PAI-1). What are the effects of lisinopril treatment on PAI-1 concentrations and the morphology and function of the ovaries in the letrozole-induced polycystic ovary syndrome (PCOS) rat model?

Design

This prospective randomized controlled animal study involved female Wistar albino rats. Twelve rats were assigned as controls (group I). In the study group (n = 48), letrozole (an aromatase inhibitor) was administered for PCOS modelling for 9 weeks. After confirming disrupted oestrous cycles, the study group was randomized into two groups: group II (n = 24; letrozole only) and group III (n = 24; letrozole + lisinopril 15 mg/kg per day). After 12 weeks, each group was divided randomly into two. Biochemical, histopathological and immunohistochemical analyses was performed in subgroups designated A, and fertilization rates were studied in subgroups designated B.

Results

Lisinopril treatment reduced the weight and area of the ovaries, the number and wall thickness of cystic follicles, and serum concentrations of LH and testosterone, relative to group II (P < 0.001). Circulating PAI-1 concentrations were significantly different among three groups (7.7 ± 0.9 ng/ml, 9.8 ± 0.7 ng/ml and 8.6 ± 0.7 ng/ml for groups IA, IIA and IIIA; P < 0.001). Pregnancy rates were 100%, 0% and 16.7% in groups IB, IIB and IIIB.

Conclusions

In the letrozole-induced rodent PCOS model, lisinopril modifies the action of letrozole, possibly by inhibition of systemic and ovarian production of PAI-1. The use of PAI-1 inhibitors deserves further investigation in understanding the pathogenesis of PCOS.

中文翻译：

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赖诺普利治疗对大鼠多囊卵巢综合征病理生理和纤溶酶原激活物抑制剂-1浓度的影响

研究问题

血管紧张素转换酶抑制导致纤溶酶原激活剂抑制剂-1 (PAI-1) 的血浆浓度显着降低。赖诺普利治疗对来曲唑诱导的多囊卵巢综合征 (PCOS) 大鼠模型中 PAI-1 浓度以及卵巢的形态和功能有何影响？

设计

这项前瞻性随机对照动物研究涉及雌性 Wistar 白化大鼠。12 只大鼠被指定为对照组（I 组）。在研究组（n =  48）中，来曲唑（一种芳香酶抑制剂）用于 PCOS 建模 9 周。在确认发情周期中断后，研究组被随机分为两组：第二组（n =  24；仅来曲唑）和第三组（n =  24；来曲唑 + 赖诺普利 15 mg/kg 每天）。12 周后，每组随机分为两组。在指定为 A 的亚组中进行生化、组织病理学和免疫组织化学分析，并在指定为 B 的亚组中研究受精率。

结果

与组 II 相比，赖诺普利治疗降低了卵巢的重量和面积、囊性卵泡的数量和壁厚以及 LH 和睾酮的血清浓度 ( P  < 0.001)。循环 PAI-1 浓度在三组之间有显着差异（IA、IIA 和 IIIA 组为 7.7 ± 0.9 ng/ml、9.8 ± 0.7 ng/ml 和 8.6 ± 0.7 ng/ml；P  < 0.001）。IB、IIB 和 IIIB 组的妊娠率为 100%、0% 和 16.7%。

结论

在来曲唑诱导的啮齿动物 PCOS 模型中，赖诺普利可能通过抑制 PAI-1 的全身和卵巢产生来改变来曲唑的作用。PAI-1 抑制剂的使用值得进一步研究以了解 PCOS 的发病机制。