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基于CXCL12/CXCR4/STAT3信号通路探讨肾必宁颗粒对IgA肾病大鼠的肾脏保护作用及机制
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| 篇名： | 基于CXCL12/CXCR4/STAT3信号通路探讨肾必宁颗粒对IgA肾病大鼠的肾脏保护作用及机制 |
| TITLE： | Exploration of the renal protective effect and mechanism of Shenbining granule on IgA nephropathy rats based on the CXCL12/CXCR4/STAT3 signaling pathway |
| 摘要： | 目的 探讨肾必宁颗粒通过调控CXC型趋化因子配体12（CXCL12）/CXC型趋化因子受体4（CXCR4）/信号转导与转录激活因子3（STAT3）信号通路对免疫球蛋白A肾病（IgAN）大鼠的肾脏保护作用及机制。方法将60只大鼠随机分为空白组（n＝12）与造模组（n＝48）。造模组大鼠采用牛血清白蛋白、四氯化碳联合脂多糖诱导IgAN模型并进行模型验证。最终共55只大鼠（空白组9只、造模组46只）纳入后续研究。将造模组大鼠随机分为模型组（n＝10）、醋酸泼尼松组[阳性对照组，6.25mg/（kg·d），n＝12]和肾必宁颗粒低、高剂量组[4.17、8.33g/（kg·d），n＝12]，每日灌胃给药/蒸馏水1次，连续4周。末次给药后，检测大鼠尿液及血清中生化指标，观察大鼠肾组织病理形态学改变，检测大鼠肾组织中IgA沉积以及CXCL12、CXCR4、STAT3mRNA和CXCL12、CXCR4、STAT3、磷酸化STAT3（p-STAT3）蛋白表达情况，并检测肾组织中白细胞介素6（IL-6）水平。结果与模型组比较，肾必宁颗粒低、高剂量组大鼠尿红细胞计数、24h尿蛋白总量以及血尿素氮、血肌酐、丙氨酸氨基转移酶水平均显著降低（P＜0.05），白蛋白水平均显著升高（P＜0.05）；肾组织病理损伤减轻，系膜区IgA沉积减少（P＜0.05）；肾组织中CXCL12、CXCR4、STAT3mRNA及其蛋白表达水平，STAT3蛋白的磷酸化水平以及IL-6水平均显著降低（P＜0.05）。结论肾必宁颗粒可能通过抑制CXCL12/CXCR4/STAT3信号通路活化，下调炎症因子IL-6表达，减轻肾脏炎症反应，进而改善肾组织病理损伤，发挥对IgAN大鼠的肾脏保护作用。 |
| ABSTRACT： | OBJECTIVE To investigate the renal protective effect and mechanism of Shenbining granule on IgA nephropathy （IgAN） rats by regulating the CXC chemokine motif ligand 12 （CXCL12）/CXC chemokine receptor 4 （CXCR4）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. METHODS A total of 60 rats were randomly assigned into blank group （n＝12） and modeling group （n＝48）. IgAN model of modeling group was induced by using bovine serum albumin， carbon tetrachloride and lipopolysaccharide， followed by model validation. Ultimately， a total of 55 rats （9 in the blank group， 46 in the modeling group） were included in the subsequent study. The rats in the modeling group were randomly divided into model group （n＝10）， prednisone acetate group [positive control group， 6.25 mg/（kg·d）， n＝12]， Shenbining granule low- and high-dose groups [4.17， 8.33 g/（kg·d）， n＝12]. They were given relevant medicine/distilled water intragastrically， once a day， for 4 consecutive weeks. After the last medication， biochemical indicators in the urine and serum of rats were measured， and pathological morphological changes in the renal tissues of rats were observed. IgA deposition in the renal tissues， as well as the mRNA expression levels of CXCL12， CXCR4 and STAT3， and the protein expression levels of CXCL12， CXCR4， STAT3 and phosphorylated STAT3 （p-STAT3） were detected. Additionally， the level of interleukin-6 （IL-6） in the renal tissue was measured. RESULTS Compared with the model group， the low-dose and high-dose Shenbining granule groups showed significantly decreased urinary red blood cell count， 24 h total urinary protein， blood urea nitrogen， serum creatinine， and alanine amino-transferase， along with increased Alb levels （P＜0.05）. Pathological damage in the renal tissues was alleviated， with reduced IgA deposition in the mesangial region （P＜0.05）； protein and mRNA expressions of CXCL12， CXCR4 and STAT3， as well as phosphorylation level of STAT3 protein and the IL-6 level， were significantly decreased in renal tissue （P＜0.05）. CONCLUSIONS Shenbining granule may exert its renal protective effects in IgAN rats by inhibiting the activation of the CXCL12/ CXCR4/STAT3 signaling pathway， downregulating the expression of inflammatory factors such as IL-6， alleviating renal inflammation， and thereby improving renal pathological damage. |
| 期刊： | 2025年第36卷第23期 |
| 作者： | 王旭；宋纯东；陈晨晨；姜浩然 |
| AUTHORS： | WANG Xu，SONG Chundong，CHEN Chenchen，JIANG Haoran |
| 关键字： | 肾必宁颗粒；IgA肾病；趋化因子；CXCL12/CXCR4/STAT3信号通路；白细胞介素6 |
| KEYWORDS： | Shenbining granule； IgA nephropathy； chemokine； CXCL12/CXCR4/STAT3 signaling pathway； interleukin-6 |
| 阅读数： | 2 次 |
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