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基于粪便代谢组学的麻黄细辛附子汤毒性作用机制研究
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| 篇名： | 基于粪便代谢组学的麻黄细辛附子汤毒性作用机制研究 |
| TITLE： | Study on the toxic mechanism of Mahuang xixin fuzi decoction based on fecal metabolomics |
| 摘要： | 目的 研究麻黄细辛附子汤（MXF）对正常小鼠的毒性作用机制。方法将48只SPF级BABL/C小鼠随机分为空白组和MXF低、中、高剂量组，每组12只。MXF低、中、高剂量组小鼠分别按照11.262、33.786、45.050g/kg的剂量灌胃给药，空白组小鼠灌胃等体积生理盐水，每日1次，连续灌胃7d，记录体质量、肛温、生存率，并检测脏器指数、血清生化因子等指标。末次给药后收集小鼠粪便样品，采用超高效液相-质谱联用（UHPLC-QE/MS）技术检测。结果与空白组相比，MXF中剂量组小鼠在给药第3～5天、MXF高剂量组小鼠给药第2～7天体质量显著低于空白组（P＜0.05）；各给药组小鼠肛温差异无统计学意义；MXF中、高剂量组小鼠的生存率分别为58.33%、50.00%。与空白组相比，MXF低、中、高剂量组小鼠的脾、肺、胸腺、肾上腺指数和肌酸激酶，MXF低、高剂量组小鼠的睾丸指数，MXF低剂量组小鼠的肌酸激酶同工酶与肌酸激酶比值，MXF中剂量组α-羟丁酸脱氢酶、乳酸脱氢酶、碱性磷酸酶，MXF中、高剂量组小鼠的尿素和胱抑素C的差异均有统计学意义（P＜0.05）。经粪便代谢组学分析发现，MXF低、中、高剂量组中苯丙酮酸、L-酪氨酸、磷脂酰胆碱、3-磷酸甘油等19个生物标志物与空白组的差异均有统计学意义。结论MXF达到一定剂量会对小鼠体质量、多脏器和血清生化指标产生不良影响，从而表现出一定的毒性作用，其作用机制可能与扰乱机体的肠道菌群代谢、引起炎症反应和造成免疫失调有关。 |
| ABSTRACT： | OBJECTIVE To study the toxic mechanism of Mahuang xixin fuzi decoction （MXF） on normal mice. METHODS Totally 48 SPF grade BABL/C mice were randomly divided into blank group， MXF low-dose， medium-dose and high-dose groups， with 12 mice in each group. MXF low-dose， medium-dose and high-dose groups were given drug intragastrically at the dose of 11.262， 33.786， 45.050 g/kg， respectively. Blank group was administered with equal volume of normal saline， once a day， for consecutive 7 d. The body weight， anal temperature and survival rate were recorded， organ index and serum biochemical factors were detected. After the last administration， fecal samples of mice were collected and detected by UHPLC-QE/MS. RESULTS Compared with blank group， the body weight was decreased significantly from the 3rd to the 5th day after administration in MXF medium-dose group， and from the 2nd to the 7th day after administration in MXF high-dose group significantly （P＜0.05）. There was no significant difference in anal temperature among the treatment groups； the average survival rates of MXF medium-dose and high-dose groups were 58.33% and 50.00%， respectively. Compared with blank group， there were significant difference in the indexes of spleen， lung， thymus， adrenal gland and creatine kinase in MXF low-dose， medium-dose and high-dose groups， the testis index in MXF low-dose and high-dose groups， the creatine kinase isoenzyme/creatine kinase ratio in MXF low-dose group， the α-hydroxybutyrate dehydrogenase， lactate dehydrogenase and alkaline phosphatase in MXF medium-dose group， the urine and cystatin C in MXF medium-dose and high-dose groups （P＜0.05）. The fecal metabonomic analysis showed that 19 biomarkers such as phenylpyruvate， L-tyrosine， phosphatidylcholine， glycerol 3-phosphate in MXF low-dose， medium-dose and high-dose groups were significantly different from those in the blank group. CONCLUSIONS When MXF reaches a certain dose， it will have adverse effects on the body weight， multiple organs and serum biochemical indicators of mice， thus showing a certain toxic effect. Its mechanism may be related to disrupting the intestinal flora metabolism， causing inflammatory reaction and immune disorders. |
| 期刊： | 2023年第34卷第02期 |
| 作者： | 王耀东；李灿；杨勇；孙启慧；容蓉 |
| AUTHORS： | WANG Yaodong，LI Can，YANG Yong，SUN Qihui，RONG Rong |
| 关键字： | 麻黄细辛附子汤；毒性作用；粪便代谢组学 |
| KEYWORDS： | Mahuang xixin fuzi decoction； toxic effects； |
| 阅读数： | 162 次 |
| 本月下载数： | 4 次 |
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