Nintedanib Treatment After Ovulation is an Effective Therapeutic Strategy for the Alleviation of Ovarian Hyperstimulation Syndrome (OHSS) in a Mouse Model.
Nintedanib Treatment After Ovulation is an Effective Therapeutic Strategy for the Alleviation of Ovarian Hyperstimulation Syndrome (OHSS) in a Mouse Model.
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排卵后尼达尼布治疗是缓解小鼠模型卵巢过度刺激综合征 (OHSS) 的有效治疗策略
DOI：
10.2147/dddt.s351292
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Kuang Y
中科院分区：
文献类型：
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作者：
Jiang S;Li W;Zhao X;Chen L;Kuang Y
目的卵巢过度刺激综合征(OHSS)是控制性卵巢过度刺激的严重并发症。在本研究中，我们希望探索酪氨酸激酶抑制剂inetedanib是否可以通过阻断血管内皮生长因子的信号转导来抑制OHSS。考虑到九替达尼已被批准用于某些疾病的治疗。我们相信九替达尼在治疗OHSS方面有重要的潜力。方法选用6~8周龄、体重相近的雌性ICR小鼠建立OHSS模型。在人绒毛膜促性腺激素(HCG)触发后12小时和24小时，皮下注射九替达尼，分析模型小鼠在hCG触发后48小时内OHSS相关的生理特性和生化指标。结果宁达尼能明显减轻卵巢过度刺激症患者的体重变化(P<0.0001)、卵巢重量(P<0.0001)、腹腔液渗出量(P<0.01)。进一步的研究证明，九替丹尼布组的黄体(数目，P<；0.001；直径，P<；0.0001)和黄体血管(P<；0.0001)的发育受到抑制。血管通透性试验显示，给药组毛细血管出血点(P<；0.0001)也明显减少。基因表达检测显示，给药组细胞间连接相关基因的表达与非OHSS诱导组相似。进一步检测凝血和血栓形成指数表明，在OHSS模型中给药九替丹尼不会增加血栓形成或出血的风险。结论九替丹尼对OHSS小鼠模型有明显的缓解和治疗作用。这些发现为今后OHSS的临床防治提供了可行的方案。此外，由于该计划可以在排卵后实施，因此不会对配子发生、受精或胚胎发育造成潜在的不利影响。
Purpose Ovarian hyperstimulation syndrome (OHSS) is a serious complication of controlled ovarian hyperstimulation. In this study, we hope to explore whether nintedanib, a tyrosine kinase inhibitor, can inhibit OHSS by blocking signaling of vascular endothelial growth factor in a mouse model. Considering that nintedanib been approved for the treatment of some diseases. We believe that nintedanib has important potential in the treatment of OHSS. Methods Female ICR mice aged 6–8 weeks with similar initial weights were used to establish the OHSS model. At 12 and 24 hours after human chorionic gonadotropin (hCG) trigger, we administered nintedanib by subcutaneous injection and analyzed the OHSS-related physiological characteristics and biochemical indices of the model mice within 48 hours after hCG-trigger. Results Nintedanib significantly alleviated the symptoms of OHSS after hCG-trigger compared with those of OHSS group (weight change, P < 0.0001; ovarian weight, P < 0.0001, peritoneal exudation level, P < 0.01). Further investigation proved that the corpus luteum (number, P < 0.001; diameter, P < 0.0001) and luteal vessel (P < 0.0001) development were inhibited in the nintedanib administration group. Then, the vascular permeability test showed that the capillary bleeding points (P < 0.0001) were also significantly reduced in nintedanib administration group. Gene expression tests demonstrated that the intercellular connection-related genes expression in the nintedanib administration group was similar to that in the no-OHSS induced group. Further detection of coagulation and thrombosis indices indicated that the nintedanib administration in the OHSS model did not increase the risk of thrombosis or bleeding. Conclusion Our study demonstrated that nintedanib can alleviate and manage the symptoms of OHSS in a mouse model. These findings identify a feasible scheme for the prevention and treatment of OHSS in clinical practice in the future. Moreover, since the scheme can be implemented after ovulation, it will not cause potential adverse effects on gametogenesis, fertilization or embryonic development.