严银银 闫敏 武香香 朱鑫 石文博 江梦园 曾华辉

中圖分类号 R285.5 文献标志码 A 文章编号 1001-0408（2021）19-2320-07

DOI 10.6039/j.issn.1001-0408.2021.19.03

摘 要 目的：研究藏红花素（CR）对雷公藤甲素（TP）致小鼠脏器损伤的保护作用，为TP配伍减毒研究提供参考。方法：将50只小鼠按体质量随机分为正常组，TP低、高剂量组（分别记为“TP-L组”“TP-H组”，300、600 μg/kg），TP低、高剂量与CR联用组（分别记为“TP-L+CR组”“TP-H+CR组”，300 μg/kg TP+100 mg/kg CR、600 μg/kg TP+100 mg/kg CR），每组10只。除正常组外，其余各组小鼠均灌胃相应药物，每天1次，连续7 d。每天称定小鼠体质量，并记录其死亡情况。末次灌胃后，处死小鼠，取其心脏、肝、肾、睾丸并计算脏器指数;测定其血清中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、尿素氮（BUN）、血肌酐（Scr）水平以及肝组织中总超氧化物歧化酶（T-SOD）活性和丙二醛（MDA）含量;观察其心脏、肝、肾、睾丸组织的病理学变化;测定其肝组织中B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）、胱天蛋白酶3（caspase-3） mRNA的相对表达量。结果：TP-L组、TP-H组、TP-L+CR组、TP-H+CR组分别有3、5、2、3只小鼠死亡，存活率分别为70%、50%、80%、70%。与正常组比较，TP-L组、TP-H组小鼠体质量（实验第7天）、心脏指数、肝指数、肾指数（TP-L组除外）睾丸指数和肝组织中T-SOD活性、Bcl-2 mRNA的相对表达量，血清中ALT（TP-L组除外）、AST（TP-L组除外）、BUN、Scr水平和肝组织中MDA含量、Bax mRNA的相对表达量、caspase-3 mRNA的相对表达量均显著升高（P<0.05或P<0.01）;心脏、肝、肾、睾丸组织均出现了明显的病理学变化。与同剂量TP单用组比较，TP与CR联用组小鼠上述指标均不同程度地改善，除TP-L+CR组小鼠的肾指数和血清中ALT水平外，差异均有统计学意义（P<0.05或P<0.01）;心脏、肝、肾、睾丸组织的病理损伤均明显改善。结论：CR可减轻TP诱导的小鼠心脏、肝、肾、睾丸的损伤，这可能与CR的抗氧化应激作用有关。

关键词 雷公藤甲素;藏红花素;配伍减毒;脏器损伤;氧化应激;小鼠

Study on Protective Effects of Crocin against Triptolide-induced Visceral Organ Injury in Mice

YAN Yinyin1，2，YAN Min2，WU Xiangxiang2，ZHU Xin3，SHI Wenbo1，2，JIANG Mengyuan2，ZENG Huahui1，2           （1. School of Medicine， Henan University of TCM， Zhengzhou 450046， China; 2. Academy of Chinese Medical Sciences， Henan University of TCM， Zhengzhou 450046， China; 3. School of Pharmacy， Henan University of TCM， Zhengzhou 450046， China）

ABSTRACT OBJECTIVE： To study the protective effects of crocin （CR） against triptolide （TP）-induced visceral organ injury in mice， and to provide reference for the studying TP compatibility and detoxification. METHODS： Fifty mice were randomly divided into normal group， TP low-dose and high-dose groups （i.e. TP-L group， TP-H group， with 300， 600 μg/kg）， TP low-dose and high dose combined with CR groups （i.e. TP-L+CR group， TP-H+CR group， with 300 μg/kg TP+100 mg/kg CR， 600 μg/kg TP+100 mg/kg CR）， with 10 mice in each group. Except for normal group， other groups were given relevant medicine intragastrically， once a day， for consecutive 7 d. The body weight of mice was weighted every day， and their death was recorded. After last administration， the mice were sacrificed， and the heart， liver， kidney and testis were taken， and the organ index was calculated; serum levels of ALT， AST， BUN and Scr， the activity of T-SOD and the contents of MDA were all determined. The pathological changes of heart， liver， kidney and testis were observed; mRNA expression of Bcl-2， Bax and caspase-3 in liver tissue were determined. RESULTS： Three， five， two and three mice in TP-L group， TP-H group， TP-L+CR group and TP-H+CR group died respectively， and the survival rates were 70%， 50%， 80% and 70%， respectively. Compared with normal group， the body weight （7th day of experiment）， heart index， liver index， kidney index （except for TP-L group）， testicular index， T-SOD activity and mRNA expression of Bcl-2 in liver tissue， serum levels of ALT （except for TP-L group）， AST （except for TP-L group）， BUN and Scr， MDA content and mRNA expression of Bax， mRNA expression of caspase-3 in liver tissue were increased significantly （P<0.05 or P<0.01）. There were obvious pathological changes in heart， liver， kidney and testis tissue. Compared with the same dose of TP alone group， the above indexes of TP combined with CR group were improved in varying degrees. Except for the renal index and serum ALT level of TP-L+CR group， there was statistical significance for all indexes（P<0.05 or P<0.01）; the pathological injuries of heart， liver， kidney and testis were significantly improved. CONCLUSIONS： CR can relieve the damage of heart， liver， kidney and testis induced by TP， which may be related to the antioxidant stress of CR.