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717解毒合剂调控巨噬细胞表型转化改善蝮蛇毒致局部组织损伤的作用及机制
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| 篇名： | 717解毒合剂调控巨噬细胞表型转化改善蝮蛇毒致局部组织损伤的作用及机制 |
| TITLE： | Effect and mechanism of 717 Jiedu decoction on Gloydius brevicaudus venom-induced local tissue injury by regulating macrophage phenotype transformation |
| 摘要： | 目的 探讨717解毒合剂调控巨噬细胞表型转化改善蝮蛇毒诱导局部组织损伤的作用及可能机制。方法通过灌胃大鼠生理盐水、尾静脉注射抗蝮蛇毒血清（0.6mL/只）以及灌胃0.495、0.99、1.98g/kg（以生药量计）717解毒合剂，制备大鼠空白/含药血清。将经佛波醇12-十四酸酯13-乙酸酯诱导分化的人白血病单核细胞源M0型巨噬细胞分为正常对照组、模型组、阳性对照组和717解毒合剂低、中、高浓度含药血清组。除正常对照组外，其余各组均加入10μg/mL蝮蛇毒工作液和10%的空白/含药血清。培养结束后，观察各组细胞超微结构变化，检测细胞中M1、M2型巨噬细胞比例，检测巨噬细胞表型转化相关标志物和缺氧诱导因子1α（HIF-1α）的mRNA及蛋白表达。结果与正常对照组比较，模型组细胞出现线粒体肿胀、嵴断裂及细胞质空泡化等超微结构损伤；细胞中M1型巨噬细胞比例及相关表型转化标志物[诱导型一氧化氮合酶、肿瘤坏死因子α、白细胞介素6（IL-6）、IL-1β]和HIF-1α的mRNA及蛋白表达水平均显著升高（P＜0.05），M2型巨噬细胞比例及相关表型转化标志物（精氨酸酶1、IL-10、甘露糖受体C1及几丁质酶-3样蛋白1）的mRNA及蛋白表达水平均显著降低（P＜0.05）；与模型组比较，717解毒合剂高浓度含药血清组细胞超微结构损伤明显改善，上述指标均显著逆转（P＜0.05）。结论717解毒合剂可通过调控M1、M2型巨噬细胞表型转化平衡、修复细胞超微结构损伤发挥抗炎及组织修复作用，其机制可能与抑制HIF-1α通路的过度激活相关。 |
| ABSTRACT： | OBJECTIVE To explore the effect and potential mechanism of 717 Jiedu decoction in ameliorating local tissue injury induced by Gloydius brevicaudus venom via regulating macrophage phenotype transformation.METHODS Rat blank-serum and drug-containing serum were prepared by intragastric administration of normal saline， tail-vein injection of anti- G. brevicaudus venom serum （0.6 mL per rat）， and intragastric administration of 717 Jiedu decoction at doses of 0.495， 0.99 and 1.98 g/kg （calculated as crude drug）. M0-type macrophages derived from human leukemia monocytic THP-1 cells induced and differentiated by PMA were divided into normal control group， model group， positive control group， and low-， medium- and high-concentration 717 Jiedu decoction drug-containing serum groups. Except for the normal control group， all other groups were treated with 10 μg/mL G. brevicaudus venom working solution and 10% blank or drug-containing serum. After the cultivation period， the cellular ultrastructural changes in each group were observed； the proportions of M1- and M2-type macrophages， as well as the mRNA and protein expression of macrophage phenotype transformation and hypoxia-inducible factor-1α （HIF-1α） were detected.RESULTS Compared with the normal control group， cells in the model group presented ultrastructural injuries including mitochondrial swelling， cristae rupture and cytoplasmic vacuolization. The proportion of M1-type macrophages and the mRNA and protein expression levels of related phenotype transformation markers [inducible nitric oxide synthase， tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β] and HIF-1α were significantly increased （ P ＜0.05），whereas the proportion of M2-type macrophages and the mRNA and protein expression levels of related phenotype transformation markers （arginase-1， IL-10， mannose receptor C type 1 and chitinase-3-like protein 1） were significantly decreased （ P ＜0.05）. Compared with the model group， cellular ultrastructural injuries were obviously alleviated， and the above-mentioned indexes were significantly reversed in the high-concentration 717 Jiedu decoction drug-containing serum group （ P ＜0.05）.CONCLUSIONS717 Jiedu decoction can exert anti-inflammatory and tissue-repairing effects by regulating the balance of M1-， M2-type macrophages phenotype transformation and repairing cellular ultrastructural damage. Its mechanism may be related to inhibiting the excessive activation of the HIF-1α pathway. |
| 期刊： | 2026年第37卷第19期 |
| 作者： | 熊文昕；罗健彪；谢永胜；刘熙；顾佳婕；王万春；董德刚 |
| AUTHORS： | XIONG Wenxin，LUO Jianbiao，XIE Yongsheng，LIU Xi，GU Jiajie，WANG Wanchun，DONG Degang |
| 关键字： | 717解毒合剂;蝮蛇毒;巨噬细胞;局部组织损伤;炎症;HIF-1α通路 |
| KEYWORDS： | 717 Jiedu decoction; Gloydius brevicaudus venom;Macrophage;local tissue injury;Inflammation;HIF-1α pathway |
| 阅读数： | 1 次 |
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