目的 研究復(fù)方甘草酸苷對高脂飲食誘導(dǎo)的肥胖大鼠睪丸的凋亡和類固醇合成功能的影響。方法 高脂飼喂50只8周齡雄性SD大鼠10周建立肥胖模型，造模結(jié)束后剔除不成功的10只后，將其隨機分為模型組和復(fù)方甘草酸苷低、中、高劑量（20、40、80 mg/kg）組，以相同周齡的雄性SD大鼠作為對照組，給予普通飼料飼養(yǎng)。給藥4周后，觀察大鼠一般情況，統(tǒng)計大鼠體質(zhì)量和體長計算Lee’s指數(shù)及睪丸指數(shù)。采用ELISA法檢測血清性激素睪酮（testosterone，T）和雌二醇（estradiol，E₂）水平；全自動生化分析儀檢測血清總膽固醇（total cholesterol，TC）、甘油三酯（triglycerides，TG）、游離脂肪酸（free fatty Acids，F(xiàn)FA）、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；蘇木素-伊紅（hematoxylin eosin，HE）染色觀察和Johnsen評分評估大鼠睪丸組織形態(tài)；TUNEL法評估睪丸細(xì)胞凋亡；免疫熒光染色（immunofluorescence，IF）和免疫印跡（Western blotting，WB）檢測睪丸組織中B細(xì)胞淋巴瘤-2（B-cell lymphoma-2，Bcl-2）、Bcl-2相關(guān)X蛋白（Bcl-2 associated X protein，Bax）、類固醇急性生成調(diào)節(jié)蛋白（synthesis acute regulatory protein，StAR）及細(xì)胞色素P450家族11亞家族A成員1（cytochrome P450 family 11 subfamily A polypeptide 1，CYP11A1）的表達。結(jié)果 不同劑量復(fù)方甘草酸苷治療均可降低大鼠體質(zhì)量和Lee’s指數(shù)，顯著提高睪丸指數(shù)；提高血清性激素T水平，降低E₂水平（P＜0.01）；降低血清生化指標(biāo)TC、TG、FFA和LDL-C水平，提高HDL-C水平（P＜0.01）；保護睪丸組織形態(tài)；抑制睪丸組織凋亡，下調(diào)Bax蛋白表達，上調(diào)Bcl-2蛋白表達（P＜0.01），上調(diào)類固醇合成相關(guān)蛋白StAR和CYP11A1的表達（P＜0.01）。結(jié)論 復(fù)方甘草酸苷可以改善肥胖相關(guān)睪丸損傷，調(diào)節(jié)血清激素和血脂水平，抑制睪丸凋亡的發(fā)生，提高睪丸類固醇合成相關(guān)蛋白的表達。

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.

R285.5

寧夏自然科學(xué)基金資助項目（2022AAC03744）；寧夏重點研發(fā)計劃項目（2022BEG03083）；國家自然科學(xué)基金資助項目（82274624）