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基于AIM2焦亡途径探讨化瘀解毒方减轻慢性肾脏病炎性损伤的作用机制
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| 篇名： | 基于AIM2焦亡途径探讨化瘀解毒方减轻慢性肾脏病炎性损伤的作用机制 |
| TITLE： | Mechanism of Huayu jiedu formula in alleviating inflammatory injury in chronic kidney disease based on AIM2 pyroptosis pathway |
| 摘要： | 目的 探讨化瘀解毒方减轻慢性肾脏病（CKD）炎性损伤的作用机制。方法将50只雄性SD大鼠随机分为假手术组（10只）、造模组（40只），后者采用单侧输尿管梗阻手术复制CKD模型。造模成功的大鼠随机分为模型组，艾沙利酮组（阳性对照）和中药低、高剂量组，每组10只。艾沙利酮组给予艾沙利酮1mg/kg，中药低、高剂量组分别给予化瘀解毒方13.7、27.4g/kg，假手术组和模型组给予等体积生理盐水，连续给药14d。采用苏木精-伊红、Masson染色观察大鼠肾组织病理形态改变。常规生化法检测血清尿素（SUr）、血清肌酐（SCr）、血清丙二醛（MDA）及超氧化物歧化酶（SOD）水平；酶联免疫吸附试验检测血清白细胞介素1β（IL-1β）、IL-6及肿瘤坏死因子α（TNF-α）水平。免疫组化、Westernblot法检测肾组织中过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）、线粒体转录因子A（TFAM）、黑色素瘤缺乏因子2（AIM2）、胱天蛋白酶1（caspase-1）、消皮素D（GSDMD）、IL-1β、IL-18的蛋白表达；实时荧光定量PCR检测AIM2的mRNA表达。结果与假手术组比较，模型组大鼠肾组织出现肾小球变形破坏、肾小管严重扩张、蓝色纤维蛋白沉积增多等病理改变；SUr、SCr、MDA、IL-1β、IL-6、TNF-α水平，AIM2、GSDMD、caspase-1、IL-1β、IL-18蛋白表达，AIM2mRNA表达均显著升高或上调（P＜0.01）；SOD水平，PGC-1α、TFAM蛋白表达均显著降低或下调（P＜0.01）。与模型组比较，各治疗组大鼠上述症状和多数指标均有所改善。结论化瘀解毒方可能通过调控AIM2焦亡途径改善肾功能，减轻肾脏炎性损伤和细胞焦亡，发挥肾脏保护作用。 |
| ABSTRACT： | OBJECTIVE To explore the mechanism of Huayu jiedu formula in regulating inflammatory injury in chronic kidney disease （CKD）. METHODS Fifty male SD rats were randomly divided into a sham surgery group （10 rats） and a modeling group （40 rats）. The CKD model was replicated in the modeling group by unilateral ureteral obstruction surgery. After successful modeling， the rats were randomly divided into model group， esaxerenone group （positive control）， and TCM low- and high-dose groups， with 10 rats in each group. The Esaxerenone group was given 1 mg/kg of esaxerenone， while the TCM low- and high-dose groups were given 13.7 and 27.4 g/kg of Huayu jiedu formula respectively， the sham surgery group and model group were given an equal volume of physiological saline， all groups were intervened continuously for 14 days. Hematoxylin eosin and Masson staining were used to observe the pathological changes in rat kidney tissue. Conventional biochemical methods were used to detect serum urea （SUr）， serum creatinine （SCr）， malondialdehyde （MDA）， and superoxide dismutase （SOD） levels； enzyme-linked immunosorbent assay was used to detect the levels of serum interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α（TNF-α）； immunohistochemistry and Western blot were used to detect the protein expression of peroxisome proliferator-activated receptor γ coactivator-1α（PGC-1α） ， mitochondrial transcription factor A （TFAM）， absent in melanoma 2（AIM2）， caspase-1， gasdermin D （GSDMD）， IL-1β and IL-18 in renal tissue； real-time fluorescence quantitative PCR was used to detect the mRNA expression of AIM2. RESULTS Compared with the sham surgery group， the renal tissue of the model group showed pathological changes such as glomerular deformation and destruction， severe tubular dilation， and increased deposition of blue fibrin； the levels of SUr， SCr， MDA， IL-1β， IL-6， TNF-α，the protein expression of AIM2， GSDMD， caspase-1， IL-1β， IL-18 ， and the mRNA expression of AIM2 were significantly increased or up-regulated （P＜0.01）； the levels of SOD， the protein expression of PGC-1α， TFAM were significantly reduced or down-regulated （P＜0.01）. Compared with the model group， all treatment groups showed improvement in the above symptoms and most indicators in rats. CONCLUSIONS Huayu jiedu formula may improve renal function， alleviate renal inflammatory damage and pyroptosis， and exert renal protective effects by regulating the AIM2 pyroptosis pathway. |
| 期刊： | 2025年第36卷第21期 |
| 作者： | 薛瑾环；武子雯；杨帆；楼芸芸；丁英钧；肖郁朋；刘籼慧；梁文杰 |
| AUTHORS： | XUE Jinhuan，WU Ziwen，YANG Fan，LOU Yunyun，DING Yingjun，XIAO Yupeng，LIU Xianhui，LIANG Wenjie |
| 关键字： | 慢性肾脏病；化瘀解毒方；黑色素瘤缺乏因子2；焦亡途径 |
| KEYWORDS： | chronic kidney disease； Huayu jiedu formula； absent in melanoma 2； pyroptosis pathway |
| 阅读数： | 2 次 |
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