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汪永辉,萧闵,李瑛,马珑,江晓翠,王岚,龚健,王武胜.参苓白术散调节AMPK、ABCG2改善高尿酸血症模型小鼠尿酸的实验研究[J].湖南中医药大学学报,2022,42(12):1982-1987[点击复制] |
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| 参苓白术散调节AMPK、ABCG2改善高尿酸血症模型小鼠尿酸的实验研究 |
| 汪永辉,萧闵,李瑛,马珑,江晓翠,王岚,龚健,王武胜 |
| (湖北中医药大学黄家湖医院, 湖北 武汉 430065;湖北中医药大学中医药实验中心, 湖北 武汉 430065;湖北中医药大学, 湖北 武汉 430065) |
| 摘要: |
| 目的 明确参苓白术散调节AMP活化蛋白激酶(AMP-activated protein kinase, AMPK)/ATP结合盒转运体G2(ATPbinding cassette transporter G2, ABCG2)通路降低高尿酸血症(hyperuricemia, HUA)模型小鼠尿酸(uric acid, UA)的作用机制。方法 将36只雄性昆明小鼠随机分为空白组、模型组、中药组、西药组4组。空白组除外,其余各组腹腔注射氧嗪酸钾悬液(0.6 g/kg)连续7 d,建立HUA小鼠模型,参苓白术散干预14 d;采用生化法检测血清UA、谷草转氨酶(aspartate aminotransaminase, AST)、谷丙转氨酶(alanine aminotransferase, ALT)含量,ELISA法检测血清半胱氨酸蛋白酶抑制剂C(cystatin C, CysC)含量,HE染色法观察肝、肾、回肠组织病理变化,Western blot检测回肠组织ABCG2、磷酸化的AMPK(phosphorylated AMPK, p-AMPK)表达,RT-qPCR检测ABCG2 m RNA表达。结果 与空白组比较,模型组UA、CysC含量均显著升高(P<0.01),p-AMPK、ABCG2蛋白及ABCG2 m RNA含量均明显降低(P<0.01)。与模型组比较,西药组和中药组UA含量均显著降低(P<0.01),p-AMPK、ABCG2蛋白及ABCG2 mRNA含量均明显升高(P<0.01);中药组CysC含量显著降低(P<0.01)。空白组肾小球大小均匀,结构清晰;模型组肾间质有炎性细胞浸润,上皮细胞轻微脱落;中药组及西药组上皮细胞脱落症状有所改善。空白组回肠组织黏膜皱襞规则,肠绒毛完整、整齐、密集;模型组肠绒毛短小,隐窝深度变浅,肠黏膜上皮细胞损伤;西药组和中药组肠黏膜上皮细胞损伤有所改善。参苓白术散对肝功能及肝组织形态均无明显损伤。结论 参苓白术散通过调节HUA小鼠肠组织AMPK磷酸化,升高ABCG2表达,降低血清UA含量以治疗HUA,且无肝功能损伤。 |
| 关键词: 高尿酸血症 参苓白术散 尿酸 半胱氨酸蛋白酶抑制剂C AMP活化蛋白激酶 ATP结合盒转运体G2 |
| DOI：10.3969/j.issn.1674-070X.2022.12.005 |
| 投稿时间：2022-09-28 |
| 基金项目:湖北省卫生健康委员会中医类面上项目(ZY2021M060) |
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| Experimental study on Shenling Baizhu Powder's effects on uric acid in hyperuricemia model mice through AMPK and ABCG2 |
| WANG Yonghui,XIAO Min,LI Ying,MA Long,JIANG Xiaocui,WANG Lan,GONG Jian,WANG Wusheng |
| (Huangjiahu Hospital of Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China;Experimental Center of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China) |
| Abstract: |
| Objective To clarify the mechanism of Shenlin Baizhu Powder(SlBZP) regulating AMP activated protein kinase(AMPK)/ATP-binding cassette transporter G2(ABCG2) pathway to reduce uric acid(UA) in hyperuricemia(HUA) model mice.Methods Thirty six male Kunming mice were randomly divided into four groups: blank group, model group, Chinese medicine group,and Western medicine group. Except the blank group, the other groups were injected intraperitoneally with potassium oxyazinate suspension(0.6 g/kg) for 7 d to establish the HUA mice model. SLBSP was then given intragastricly for 14 d. After the above intervention, the content of serum UA, aspartate aminotransferase(AST) and alanine aminotransferase(ALT) were detected by biochemical method; the content of serum cystatin C(CysC) was detected by ELISA, and the histopathological changes of liver, kidney and ileum were observed by HE staining. The expression levels of ABCG2 and phosphorylated AMPK(p-AMPK) in ileum were detected by Western blot, and the mRNA expression levels of ABCG2 were detected by RT-qPCR.Results Compared with the blank group, the serum UA and CysC content in the model group significantly increased(P<0.01), and the content of p-AMPK, ABCG2 and ABCG2mRNA in the model group were significantly reduced(P <0.01). Compared with the model group, the serum UA in the western medicine group and the Chinese medicine group were significantly reduced(P<0.01), while the content of p-AMPK, ABCG2 and ABCG2 m RNA significantly increased(P<0.01). Compared with the model group, the serum CysC in the chinese medicine group was significantly reduced(P<0.01). In the blank group, the glomeruli were uniform in size, and clear in structure. In the model group,inflammatory cell infiltration existed in the renal interstitium, and epithelial cells slightly shed. The symptoms of epithelial cell shedding in the Chinese medicine group and the western medicine group were improved. The mucosal folds of the ileal tissue in the blank group were regular, and the intestinal villi were complete, neat and dense. In the model group, the intestinal villi were short, and the crypt depth became shallow. The epithelial cells of the intestinal mucosa in the model group were damaged. The damage condition of intestinal mucosal epithelial cells in the Chinese medicine group and the western medicine group improved.The evaluation showed that SLBZP has brought no obvious damage to liver function and liver tissue morphology.Conclusion SlBZP can reduce serum UA and increase ABCG2 expression by regulating AMPK phosphorylation of intestinal tissues of HUA mice,without affecting liver function. |
| Key words: hyperuricemia Shenling Baizhu Powder uric acid cystatin C AMP-activated protein kinase ATP-binding cassette transporter G2 |
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