虫草素预防肥胖及通过ADORA1介导GH3细胞中泌乳素分泌研究

为了研究虫草素是否具有预防肥胖的作用及其可能机制，试验利用高脂饮食诱导肥胖型高脂血症大鼠动物模型，并给予高、中、低不同剂量（50、25、12.5 mg/（kg·d））的虫草素，连续灌胃35 d后观察大鼠体重、脂肪系数、血脂水平的变化；体外培养大鼠脑垂体瘤细胞（GH3），通过CCK8、Western blotting、ELISA等方法检测虫草素对GH3细胞的增殖毒性，以及腺苷受体A₁（ADORA₁）的表达和对泌乳素分泌量的影响。体内试验结果显示，与正常对照组相比，模型组大鼠体重、脂肪系数和血脂水平（高密度脂蛋白（HDL）除外）均极显著升高（P<0.01）；虫草素高、中、低各剂量组均能极显著或显著降低大鼠体重、脂肪系数及总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）水平（P<0.01；P<0.05），但HDL水平仅在虫草素高剂量组中显著升高（P<0.05），而虫草素中、低剂量组均无显著变化（P>0.05）；体外试验结果显示，虫草素浓度低于25 μg/mL时对GH3细胞增殖无影响；虫草素能够诱导GH3细胞ADORA₁表达升高；虫草素和ADORA₁激动剂（R-PIA）单独作用能显著或极显著降低泌乳素的分泌量（P<0.05；P<0.01），虫草素与ADORA₁抑制剂（DPCPX）联合作用时能够在一定程度上阻断虫草素对泌乳素的抑制作用。结果表明，虫草素具有预防肥胖和降血脂的作用，其可能的作用机制是通过诱导ADORA₁表达抑制泌乳素的分泌，该研究结果将为虫草素作为一种潜在的减肥降脂药物的开发提供一定依据。

Study on Cordycepin Prevents Obesity and Mediates Prolactin Secretion Through ADORA1 in GH3 Cells

To investigate the effect of cordycepin on preventing obesity and its possible mechanism,high-fat-diet induced rat models were used.Experimental groups were given daily oral administration of cordycepin at different concentrations (50,25 and 12.5 mg/(kg·d)) for 35 days.Subsequently,body weight,fat weight and serum lipids of obese rats induced by high-fat diet were selected as the indexes to observe the effect of different dosages of cordycepin on preventing obesity.The role of cordycepin on cell proliferation,expression of adenosine receptor A₁ (ADORA₁) and the secretion of prolactin were detected by CCK8,Western blotting and ELISA in GH3 cells.The results in vivo showed that compare with normal control group,the body weight,fat weight and the level of serum lipids(except HDL) in modle rats were extremely significantly incresed (P<0.01),the body weight,fat weight,and the levels of TC,TG and LDL in rats administrated with cordycepin were extremely significantly or significantly reduced (P<0.01;P<0.05),and the level of HDL was significantly increased in high-dose cordycepin group (P<0.05),there was no significant difference between low-dose cordycepin and middle-dose groups (P>0.05).The results in vitro showed that it had no effect on the proliferation when the concentration of cordycepin was lower than 25 μg/mL in GH3 cells;The expression of ADORA₁ in GH3 cells was increased by cordycepin induction,the secretion of prolactin could be significantly or extremely significantly reduced by cordycepin and ADORA₁ agonist (R-PIA) (P<0.05;P<0.01),but its effect could be blocked by ADORA₁ inhibitor (DPCPX).In conclusion,cordycepin could prevent obesity and reduce serum lipids,which might be related to inhibiting the secretion of prolactin by ADORA₁.The results would lay a theoretical foundation for the development of anti-obesity drugs.