目的 探究梓醇調(diào)節(jié)Hedgehog通路對早發(fā)性卵巢功能不全（POI）大鼠的卵巢保護作用。方法 將大鼠隨機分為對照組，模型組，梓醇低、高劑量（30、60 mg·kg^-1）組，梓醇（60 mg·kg^-1）＋GANT-61（40 mg·kg^-1，Hedgehog通路抑制劑）組，除對照組外，每天ig 1次50 mg·kg^-1的雷公藤多苷混懸液，連續(xù)14 d，制備POI模型，模型成功后每天ip給藥1次，連續(xù)給藥4周。取卵巢組織計算大鼠卵巢指數(shù)；ELISA測定血清激素雌二醇（E₂）、黃體生成素（LH）和卵泡刺激素（FSH）水平；試劑盒檢測卵巢組織中活性氧（ROS）、丙二醛（MDA）、超氧化物歧化酶（SOD）和過氧化物酶（CAT）水平；HE染色觀察卵巢組織結構并進行卵泡計數(shù)；TUNEL檢測卵巢組織細胞凋亡情況；Western blotting檢測卵巢組織cleaved Caspase-3、Bax、Bcl-2、Shh、Gli1蛋白表達。結果 與對照組比較，模型組大鼠卵巢組織形態(tài)明顯損傷，卵巢指數(shù)、血清E₂水平、卵巢組織中SOD和CAT水平、生長卵泡數(shù)量、Bcl-2、Shh、Gli1蛋白表達水平顯著降低（P＜0.05），血清FSH和LH水平、卵巢組織中ROS和MDA水平、閉鎖卵泡數(shù)量、細胞凋亡率、cleaved Caspase-3和Bax蛋白表達水平顯著升高（P＜0.05）；與模型組相比，梓醇30、60 mg·kg^-1組大鼠卵巢組織形態(tài)損傷明顯減輕，卵巢指數(shù)、血清E₂水平、卵巢組織中SOD和CAT水平、生長卵泡數(shù)量、Bcl-2、Shh、Gli1蛋白表達水平顯著升高（P＜0.05），血清FSH和LH水平、卵巢組織中ROS和MDA水平、閉鎖卵泡數(shù)量、細胞凋亡率、cleaved Caspase-3和Bax蛋白表達水平顯著降低（P＜0.05）；GANT-61可減輕梓醇對POI大鼠卵巢的保護作用（P＜0.05）。結論 梓醇可降低POI大鼠卵巢組織氧化應激、細胞凋亡，調(diào)控血清激素水平，進而改善卵巢功能，可能是通過激活Hedgehog通路實現(xiàn)的。

Objective To investigate the ovarian protective effect of catalpol on premature ovarian insufficiency (POI) rats by regulating the Hedgehog pathway. Methods Rats were randomly grouped into control group, model group, catalpol low and high dose（30 and 60 mg·kg^-1）group, and catalpol (60 mg·kg^-1) + GANT-61 (Hedgehog pathway inhibitor, 40 mg·kg^-1) group. Except for the control group, a 50 mg·kg^-1 suspension of Tripterygium glycosides was administered orally once a day for 14 consecutive days to prepare a POI model. After the model was successful, it was administered via ip once a day for four consecutive weeks. The wet weight and ovarian index of rat ovaries were calculated. ELISA was applied to measure serum hormones estradiol (E₂), luteinizing hormone (LH), and follicle stimulating hormone (FSH). The reagent kits were applied to detect reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and peroxidase (CAT) in ovarian tissue. HE staining was applied to observe ovarian tissue structure and perform follicle counting. TUNEL was applied to detect apoptosis in ovarian tissue cells. Western blottinng was applied to detect the expression of Cleaved caspase-3, Bax, Bcl-2, Shh, and Gli1 proteins in ovarian tissue. Results Compared with the control group, the ovarian tissue morphology of rats in the model group was obviously damaged, the ovarian index, serum E₂ level, SOD and CAT levels in ovarian tissue, number of growing follicles, and Bcl-2, Shh, and Gli1 protein expression levels were obviously reduced (P < 0.05), the serum FSH and LH levels, ROS and MDA levels in ovarian tissue, number of atresia follicles, cell apoptosis rate, and Cleaved caspase-3 and Bax protein expression levels were obviously increased (P < 0.05). Compared with the model group, the morphological damage of ovarian tissue of rats in the catalpol groups was obviously reduced, the ovarian index, serum E₂ level, SOD and CAT levels in ovarian tissue, number of growing follicles, and Bcl-2, Shh, and Gli1 protein expression levels were obviously increased (P < 0.05), the serum FSH and LH levels, ROS and MDA levels in ovarian tissue, number of atresia follicles, cell apoptosis rate, and Cleaved caspase-3 and Bax protein expression levels were obviously reduced (P < 0.05). GANT-61 was able to alleviate the protective effect of catalpol on the ovaries of POI rats (P < 0.05). Conclusion Catalpol can reduce oxidative stress and cell apoptosis in ovarian tissue of POI rats, regulate serum hormone level, and thereby improve ovarian function, which is possibly achieved by activating the Hedgehog pathway.

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國家自然科學基金資助項目（82174212、82104917）;山東省自然科學基金青年項目（ZR2022QH075）