文献类型：期刊文献

中文题名：归芪益元膏通过NLRP3/ASC/caspase-1通路调控^(12)C^(6+)束辐射肺肾旁效应损伤大鼠的机制

英文题名：Mechanism of Guiqi Yiyuan Ointment in regulating the lung and kidney injury of^(12)C^(6+)beam radiation-bystander effect in rats through NLRP3/ASC/caspase-1 pathway

作者：马天星[1];李金田[1,2];李娟[3];张毅[1];梁建庆[2,3];陈世玉[1];张悦[1];姜佳辰[1];徐韦玮[1]

第一作者：马天星

机构：[1]甘肃中医药大学中医临床学院,兰州730000;[2]敦煌医学与转化教育部重点实验室,兰州730000;[3]甘肃中医药大学基础医学院,兰州730000

第一机构：甘肃中医药大学中医临床学院

年份：2024

卷号：39

期号：10

起止页码：5162

中文期刊名：中华中医药杂志

外文期刊名：China Journal of Traditional Chinese Medicine and Pharmacy

收录：CSTPCD;;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金项目(No.8216150493);甘肃省教育厅“双一流”科研重点项目(No.GSSYLXM-05);甘肃省中医药研究中心开放课题(No.zyzx-2020-zx17)。

语种：中文

中文关键词：肺;肾;旁效应;归芪益元膏;^(12)C^(6+)束;炎症小体;辐射;活性氧

外文关键词：Lung;Kidney;Bystander effects;Guiqi Yiyuan Ointment;^(12)C^(6+)beam radiation;Inflammatorysomes;Radiation;Reactive oxygen species(ROS)

摘要：目的:观察归芪益元膏对辐射肺肾旁效应损伤大鼠的影响,从ROS介导的NLRP3/ASC/caspase-1通路探讨其作用机制。方法:70只Wistar大鼠随机分为空白组,模型组,抑制剂组,西药组,中药高、中、低剂量组,每组10只。照射前中药高、中、低剂量组分别预先灌胃4.8、2.4、1.2g/kg归芪益元膏14d;抑制剂组预先腹腔注射ROS抑制剂乙酰半胱氨酸7d(40mg/200g);西药组辐射前30min腹腔单次注射氨磷汀(28 mg/200 g),空白组及模型组给予等体积0.9%氯化钠溶液,第15天除空白组外各组大鼠右肺4 Gy^(12)C^(6+)束单次照射。3 d后取血清、肾组织,HE染色检测病理变化,免疫荧光检测ROS表达,ELISA法测血清ROS、IL-1β、IL-18、TNF-α含量,血清BUN、Cr水平,PCR检测肾组织NLRP3、ASC、caspase-1、NF-κB p65 mRNA表达,Western Blot检测NLRP3、ASC、caspase-1、p-NF-κB p65/NF-κB p65蛋白表达。结果:与空白组比较,模型组大鼠肾组织ROS水平均升高(P<0.05);血清ROS、IL-1β、IL-18、TNF-α、BUN、Cr水平均显著升高(P<0.05);肾组织中NLRP3、ASC、caspase-1、NF-κB p65 mRNA及NLRP3、ASC、caspase-1、p-NF-κB p65/NF-κB p65蛋白表达量均显著升高(P<0.05)。与模型组比较,各给药组大鼠肾组织中ROS水平显著降低(P<0.05);血清ROS、IL-1β、IL-18、TNF-α含量均显著下降(P<0.05);BUN、Cr水平不同程度降低;肾中NLRP3、ASC、caspase-1、NF-κB p65 mRNA及NLRP3、ASC、caspase-1、p-NF-κB p65/NF-κB p65蛋白表达均有不同程度下降。结论:归芪益元膏能有效减轻辐射及肺肾旁效应损伤作用,其机制可能与ROS介导的NLRP3炎症小体活化相关。
Objective:To observe the effects of Guiqi Yiyuan Ointment on lung and kidney injury in rats with radiation bystander effect,and to explore its mechanism through NLRP3/ASC/caspase-1 pathway mediated by reactive oxygen species(ROS).Methods:Seventy Wistar rats were randomly divided into blank group,model group,inhibitor group,Western medicine group and Chinese medicine high,middle and low dose group,with 10 rats in each group.Before irradiation,the high,middle and low doses of Chinese medicine were gavaged Guiqi Yiyuan Ointment as follows:4.8,2.4,1.2 g/kg,respectively for 14 days.In the inhibitor group,ROS inhibitor acetylcysteine was intraperitoneally injected for 7 days(40 mg/200 g).The western medicine group was given a single intrabitoneal injection of amifotene(28 mg/200 g)30 min before radiation,and the blank and model groups were given equal volume of normal saline.On the 15th day,except the blank group,the right lung of rats in each group was irradiated by a single beam of 4 Gy^(12)C^(6+).After 3 d,the serum and kidney tissues were collected,and pathological changes were detected by HE staining,ROS expression was detected by immunofluorescence,the contents of ROS,IL-1β,IL-18 and TNF-αin serum were measured by ELISA,and the levels of BUN and Cr in serum were detected.The mRNA expression of NLRP3,ASC,caspase-1 and NF-κB p65 in renal tissue were detected by PCR,and the protein expression of NLRP3,ASC,caspase-1 and p-NF-κB p65/NF-κB p65 were detected by Western Blot.Results:Compared with blank group,ROS levels in renal tissue of model group were increased(P<0.05).Serum ROS,IL-1β,IL-18,TNF-α,BUN and Cr levels were increased(P<0.05).The mRNA and protein expressions of NLRP3,ASC,caspase-1 and p-NF-κB p65/NF-κB p65 in renal tissues were increased(P<0.05).Compared with model group,ROS level in kidney of rats in each administration group was decreased(P<0.05).Serum ROS,IL-1β,IL-18 and TNF-αcontents were decreased(P<0.05).BUN and Cr levels were decreased;The mRNA and protein expressions of NLRP3,ASC,caspase-1,p-NF-κB p65/NF-κB p65 in kidney were decreased to varying degrees.Conclusion:Guiqi Yiyuan Ointment can effectively reduce the damage caused by radiation and paraprenal effect,and its mechanism may be related to the activation of NLRP3 inflammasome mediated by ROS.