目的 研究复方甘草酸苷对高脂饮食诱导的肥胖大鼠睾丸的凋亡和类固醇合成功能的影响。方法 高脂饲喂50只8周龄雄性SD大鼠10周建立肥胖模型，造模结束后剔除不成功的10只后，将其随机分为模型组和复方甘草酸苷低、中、高剂量（20、40、80 mg/kg）组，以相同周龄的雄性SD大鼠作为对照组，给予普通饲料饲养。给药4周后，观察大鼠一般情况，统计大鼠体质量和体长计算Lee’s指数及睾丸指数。采用ELISA法检测血清性激素睾酮（testosterone，T）和雌二醇（estradiol，E₂）水平；全自动生化分析仪检测血清总胆固醇（total cholesterol，TC）、甘油三酯（triglycerides，TG）、游离脂肪酸（free fatty Acids，FFA）、低密度脂蛋白（low density lipoprotein cholesterol，LDL-C）和高密度脂蛋白（high density lipoprotein cholesterol，HDL-C）水平；苏木素-伊红（hematoxylin eosin，HE）染色观察和Johnsen评分评估大鼠睾丸组织形态；TUNEL法评估睾丸细胞凋亡；免疫荧光染色（immunofluorescence，IF）和免疫印迹（Western blotting，WB）检测睾丸组织中B细胞淋巴瘤-2（B-cell lymphoma-2，Bcl-2）、Bcl-2相关X蛋白（Bcl-2 associated X protein，Bax）、类固醇急性生成调节蛋白（synthesis acute regulatory protein，StAR）及细胞色素P450家族11亚家族A成员1（cytochrome P450 family 11 subfamily A polypeptide 1，CYP11A1）的表达。结果 不同剂量复方甘草酸苷治疗均可降低大鼠体质量和Lee’s指数，显著提高睾丸指数；提高血清性激素T水平，降低E₂水平（P＜0.01）；降低血清生化指标TC、TG、FFA和LDL-C水平，提高HDL-C水平（P＜0.01）；保护睾丸组织形态；抑制睾丸组织凋亡，下调Bax蛋白表达，上调Bcl-2蛋白表达（P＜0.01），上调类固醇合成相关蛋白StAR和CYP11A1的表达（P＜0.01）。结论 复方甘草酸苷可以改善肥胖相关睾丸损伤，调节血清激素和血脂水平，抑制睾丸凋亡的发生，提高睾丸类固醇合成相关蛋白的表达。

Objective To investigate the impact of compound glycyrrhizin (CG) on testicular cell apoptosis and steroid hormone synthesis in rats with obesity induced by a high-fat diet (HFD). Methods A total of 50 male SD rats, aged eight weeks, were HFD fed for 10 weeks to establish an obesity model. Excluding 10 unsuccessful models, the remaining rats were randomly assigned to either a model group or groups receiving low-, medium- and high-doses (20, 40, 80 mg/kg) of CG. The control group of SD rats of the same age was fed a regular diet. After four weeks of treatment, the rats’ general health was assessed, and their body weight and length were measured to calculate Lee’s index and testicular index. Serum levels of testosterone (T) and estradiol (E₂) were measured using ELISA. Levels of total cholesterol (TC), triglycerides (TG), free fatty acids (FFA), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined using an automatic biochemical analyzer. Testicular morphology was observed using hematoxylin-eosin (HE) staining, and Johnsen scores were evaluated. Apoptosis of testicular cells was assessed using the TUNEL method. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), steroidogenic acute regulatory protein (StAR), and cytochrome P450 family 11 subfamily A polypeptide 1 (CYP11A1) in testicular tissue was detected by immunofluorescence staining (IF) and Western blotting (WB). Results CG treatment at all doses led to a reduction in body weight and Lee's index in rats, while significantly increasing the testicular index and serum T levels, and decreasing E₂ levels (P < 0.01). Additionally, CG treatment notably lowered TC, TG, FFA, and LDL-C, while increasing HDL-C levels (P < 0.01). Histological analysis revealed that CG preserved the normal architecture of testicular tissue morphology. Moreover, CG effectively inhibited apoptosis of testicular germ cells, reduced the expression of Bax protein, and increased the expression of Bcl-2 protein (P < 0.01). It also significantly upregulated the expression of StAR and CYP11A1 (P < 0.01). Conclusion CG can mitigate testicular damage associated with obesity, normalize serum hormone and lipid levels, prevent testicular apoptosis, and enhance the expression of proteins involved in testicular steroid synthesis.

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宁夏自然科学基金资助项目（2022AAC03744）；宁夏重点研发计划项目（2022BEG03083）；国家自然科学基金资助项目（82274624）