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银杏叶提取物对糖尿病肾病模型小鼠肾脏炎症的抑制作用及机制
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| 篇名： | 银杏叶提取物对糖尿病肾病模型小鼠肾脏炎症的抑制作用及机制 |
| TITLE： | Inhibitory effects of Ginkgo biloba extract on renal inflammation in diabetic nephropathy model mice and its mechanism |
| 摘要： | 目的 探讨银杏叶提取物（GBE）抑制糖尿病肾病（DN）模型小鼠肾脏炎症的作用及其可能机制。方法以高脂高糖喂养KK/Ay小鼠建立DN模型，并分为模型组、阳性对照组[二甲双胍200mg/（kg·d）]和GBE低、高剂量组[100、200mg/（kg·d）]，每组6只；另取普通饲料喂养的C57BL/6J小鼠6只，作为对照组。各药物组小鼠灌胃相应药液，对照组和模型组小鼠灌胃等体积生理盐水，每天1次，连续8周。检测小鼠的体重、空腹血糖、24h摄食量、24h尿量和血清单核细胞趋化蛋白1（MCP-1）、白细胞介素12（IL-12）、IL-10、晚期糖基化终末产物（AGEs）、血尿素氮（BUN）、血肌酐（Scr）水平，计算其双侧肾脏质量与体重的比值，观察其肾皮质的病理损伤和纤维化改变，并检测其肾皮质中巨噬细胞极化标志蛋白[M1型：诱导型一氧化氮合酶（iNOS）；M2型：精氨酸酶1（Arg-1）]和AGEs-晚期糖基化终末产物受体（RAGE）/Ras同源基因家族成员A（RhoA/）/Rho相关螺旋卷曲蛋白激酶（ROCK）信号通路相关蛋白的表达情况。结果与模型组比较，GBE低、高剂量组小鼠肾皮质增生、空泡、炎症细胞浸润、肾皮质纤维化等症状均有所好转；其体重、血清IL-10水平、肾皮质中Arg-1蛋白的表达水平均显著高于模型组（P＜0.01）；空腹血糖和24h摄食量、尿量，血清MCP-1、IL-12、BUN、Scr、AGEs水平，双侧肾脏质量与体重的比值，肾损伤评分和肾间质纤维化比例，肾皮质中iNOS、RAGE、RhoA、ROCK1（GBE低剂量组除外）蛋白的表达水平均显著低于模型组（P＜0.01）。结论GBE可改善DN模型小鼠的肾损伤，并减轻其炎症反应，其机制可能与抑制AGEs-RAGE/RhoA/ROCK信号通路、调节巨噬细胞极化有关。 |
| ABSTRACT： | OBJECTIVE To investigate the inhibitory effects of Ginkgo biloba extract （GBE） on renal inflammation in diabetic nephropathy （DN） model mice， and its potential mechanism. METHODS KK/Ay mice were fed with high fat and high sugar to induce DN model. They were divided into model group， positive control group [metformin 200 mg/（kg·d）]， GBE low-dose and high-dose groups [100， 200 mg/（kg·d）]， with 6 mice in each group. Six C57BL/6J mice were fed with a regular diet as the control group. Administration groups were given relevant liquid intragastrically， control group and model group were given constant volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The body weight， fasting blood glucose， 24-hour food intake， 24-hour urine output， monocyte chemoattractant protein-1 （MCP-1）， interleukin-12 （IL-12）， IL-10， advanced glycation end products （AGEs）， blood urea nitrogen （BUN） and serum creatinine （Scr） of mice were measured， and the ratio of bilateral kidneys to body weight was also calculated. The pathological injury and fibrotic changes of the renal cortex were observed， and the expressions of macrophage polarization marker proteins [type M1： inducible nitric oxide synthase （iNOS）； type M2： arginase-1 （Arg-1）] and AGEs-the receptor of advanced glycation end products （RAGE）/Ras homolog gene pharm_chenjing@163.com family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway-related proteins were determined in renal cortex. RESULTS Compared with the model group， the symptoms such as renal cortical hyperplasia， vacuoles， infiltration of inflammatory cells， and renal cortical fibrosis had been improved in GBE low-dose and high-dose groups； body weight， serum level of IL-10， the expression of Arg-1 in the renal cortex were significantly higher than model group （P＜ 0.01）； fasting blood glucose， 24-hour food intake， 24-hour urine output， serum levels of MCP-1， IL-12， BUN， Scr and AGEs， the ratio of bilateral kidneys to body weight， renal injury score， the proportion of renal interstitial fibrosis， the protein expressions of iNOS， RAGE， RhoA and ROCK1 （except for GBE low-dose group） in renal cortex were significantly lower than model group （P＜0.01）. CONCLUSIONS GBE could improve kidney damage and alleviate inflammatory response in DN model mice， the mechanism of which may be related to inhibiting the AGEs-RAGE/RhoA/ROCK signaling pathway and regulating macrophage polarization. |
| 期刊： | 2024年第35卷第02期 |
| 作者： | 陈璟；杨小艺；陈静；单鑫；汪洁；许惠琴；吕志阳 |
| AUTHORS： | CHEN Jing，YANG Xiaoyi，CHEN Jing，SHAN Xin，WANG Jie，XU Huiqin，LYU Zhiyang |
| 关键字： | 银杏叶提取物；糖尿病肾病；炎症反应；巨噬细胞极化；晚期糖基化终末产物-晚期糖基化终末产物受体/Ras同源基因家 |
| KEYWORDS： | Ginkgo biloba extract； diabetic nephropathy； inflammation； macrophage polarization； AGEs-RAGE/RhoA/ROCK |
| 阅读数： | 31 次 |
| 本月下载数： | 3 次 |
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