目的: 探讨Kindlin-2对小鼠子宫发育及雌鼠生育能力的影响及其作用机制。方法: 利用Cdh16-Cre工具鼠和Kindlin-2^flox/flox小鼠构建在子宫内膜中特异性敲除Kindlin-2的小鼠模型，观察敲除Kindlin-2对雌鼠子宫内膜发育和生殖力的影响。在子宫内膜癌细胞系HEC-1和Ish中分别进行高表达和敲低Kindlin-2的实验，检测雷帕霉素靶蛋白(mammalian target of rapamycin，mTOR)信号通路的激活变化，并且提取特异性敲除Kindlin-2的雌鼠(实验组，基因型为Cdh16-Cre; Kindlin-2^flox/flox)和未特异性敲除Kindlin-2的雌鼠(对照组，基因型为Kindlin-2^flox/flox)子宫蛋白，每组包含6~8只小鼠，重复3次独立实验，检测mTOR信号通路和Hippo信号通路关键分子的蛋白水平。结果: 成功构建了子宫内膜特异性敲除Kindlin-2的小鼠模型，通过鼠尾聚合酶链式反应(polymerase chain reaction，PCR)、Western blot、免疫组织化学染色(immunohistochemistry，IHC)等方法鉴定和验证Kindlin-2在小鼠子宫中的敲除效率。子宫内膜特异性敲除Kindlin-2的雌鼠与对照组相比体质量减轻、生殖能力严重受损、出生仔鼠数量减少，但出生仔鼠中雌鼠和雄鼠的比例未发生改变，通过苏木精-伊红染色实验观察表明实验组子宫内膜发育不完整、子宫壁厚度变薄。机制方面，子宫内膜癌细胞系HEC-1和Ish中敲除Kindlin-2能够下调mTOR、磷酸化mTOR、腺嘌呤核糖核苷酸激活蛋白激酶(adenosine monophosphate-activated protein kinase，AMPK)、磷酸化的AMPK和磷酸化的核糖体蛋白(ribosomal protein S6，S6)的蛋白水平，在雌鼠子宫中发现特异性敲除Kindlin-2能够上调Mps结合1(Mps one binding 1，MOB1)、磷酸化的Yes相关蛋白(Yes-associated protein，YAP)的蛋白水平。结论: Kindlin-2通过抑制mTOR信号通路、激活Hippo信号通路抑制子宫内膜的发育，进而抑制雌鼠的生育能力。

Objective: To investigate the effects and mechanisms of Kindlin-2 on uterus development and reproductive capacity in female mice. Methods: Cdh16-Cre tool mice and Kindlin-2^flox/flox mice were used to construct the mouse model of uterus specific knockout of Kindlin-2, and the effects of Kindlin-2 deletion on uterine development and reproduction capacity of female mice were observed. High expression and knockdown of Kindlin-2 in endometrial cancer cell lines HEC-1 and Ish were used to detect the regulation of mammalian target of rapamycin (mTOR) signaling pathway. In addition, uterine proteins of the female mice with specific knockout of Kindlin-2 and female mice in the control group were extracted to detect the protein levels of key molecules of mTOR signaling pathway and Hippo signaling pathway. Results: The mouse model of uterine specific knockout of Kindlin-2 was successfully constructed. The knockout efficiency of Kindlin-2 in mouse uterus was identified and verified by mouse tail polymerase chain reaction (PCR), Western blot protein identification, immunohistochemical staining (IHC) and other methods. Compared with the control group, the female mice with uterus specific deletion of Kindlin-2 lost weight, seriously impaired reproductive ability, and the number of newborn mice decreased, but the proportion of the female mice and male mice in the newborn mice did not change. Hematoxylin eosin staining (HE) experiment showed that the endometrium of Kindlin-2 knockout group was incomplete and the thickness of uterine wall became thinner. In terms of mechanism, the deletion of Kindlin-2 in endo-metrial cancer cell lines HEC-1 and Ish could downregulate the protein levels of mTOR, phosphorylated mTOR, adenosine monophosphate-activated protein kinase (AMPK), phosphorylated AMPK and phosphorylated ribosomal protein S6 (S6), and the mTOR signal pathway was inhibited. It was found that the specific deletion of Kindlin-2 could upregulate the protein levels of Mps one binding 1 (MOB1) and phosphorylated Yes-associated protein (YAP) in the uterus of the female mice, and the Hippo signal pathway was activated. Conclusion: Kindlin-2 inhibits the development of uterus by inhibiting mTOR signal pathway and activating Hippo signal pathway, thereby inhibiting the fertility of female mice.