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石淋清颗粒预防大鼠草酸钙肾结石形成的作用机制研究
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| 篇名： | 石淋清颗粒预防大鼠草酸钙肾结石形成的作用机制研究 |
| TITLE： | Study on the mechanism of Shilinqing granules preventing the formation of calcium oxalate kidney stones in rats |
| 摘要： | 目的 探讨石淋清颗粒预防大鼠草酸钙肾结石形成的作用机制。方法将60只大鼠随机分为空白组、模型组和石淋清颗粒低、中、高剂量组（6.5、13、26g/kg）及去乙酰化酶3（SIRT3）抑制剂组（石淋清颗粒26g/kg+SIRT3抑制剂25mg/kg），每组10只。除空白组外，其余各组大鼠将饮水更换为1%乙二醇溶液，并每天灌胃2%氯化铵溶液2mL，连续4周，以复制肾结石大鼠模型。造模同时，给药组灌胃相应药物，空白组和模型组灌胃等体积生理盐水。测定大鼠24h尿量、尿液pH值和尿液中Ca2+、草酸（Ox）含量及血清中肌酐（Cr）、血尿素氮（BUN）、Ca2+含量；观察大鼠肾组织病理学形态、草酸钙肾结晶情况和超微结构；检测大鼠肾组织中丙二醛（MDA）、超氧化物歧化酶（SOD）、活性氧（ROS）、骨桥蛋白（OPN）水平；检测大鼠肾组织中SIRT3、叉头框蛋白O3a（FOXO3a）、SOD2mRNA和蛋白的表达水平。结果与空白组比较，模型组大鼠24h尿量、尿液pH值、肾组织中SOD水平，以及SIRT3、FOXO3a、SOD2mRNA和蛋白表达水平均显著降低（P＜0.05或P＜0.01）；尿液中Ca2+、Ox含量，血清中Cr、BUN、Ca2+含量，肾组织中ROS、MDA、OPN水平均显著升高（P＜0.01）；肾组织病理损伤严重，可见大量弥漫性分布的黑色结晶，肾小球基膜增厚，足突细胞和肾小管上皮细胞中的线粒体水肿。与模型组比较，石淋清颗粒各剂量组大鼠上述指标含量/水平（低剂量组血清中Ca2+含量除外）均显著逆转（P＜0.05或P＜0.01），肾组织病理损伤、草酸钙肾结晶、肾小球足突细胞和肾小管上皮细胞中的线粒体损伤均明显改善；而SIRT3抑制剂组上述指标变化差异无统计学意义（P＞0.05）。结论石淋清颗粒可有效抑制大鼠草酸钙肾结石的形成，改善肾损伤，其作用机制可能与提高抗氧化作用和激活SIRT3/FOXO3a信号通路有关。 |
| ABSTRACT： | OBJECTIVE To investigate the mechanism of Shilinqing granules preventing the formation of calcium oxalate kidney stones in rats. METHODS Sixty rats were randomly divided into blank group， model group， Shilingqing granules low- dose， medium-dose and high-dose groups （6.5， 13， 26 g/kg）， SIRT3 inhibitor group （Shilingqing granules 26 g/kg+SIRT3 inhibitor 25 mg/kg）， with 10 rats in each group. Except for blank group， other groups were given 1% ethylene glycol solution instead of drinking water， and intragastrical administration of 2% ammonium chloride solution 2 mL， for 4 consecutive weeks， to induce kidney stones rat model； at the same time， administration groups were given relevant medicine intrgastrically， blank group and model group were given constant volume of normal saline intrgastrically. The 24 h urine volume， urine pH， urine contents of Ca2+ and oxalic acid （Ox）， serum contents of creatinine （Cr）， blood urea nitrogen （BUN） and Ca2+ were all determined； the renal histopathology， calcium oxalate crystallization and ultrastructure were observed； the levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， reactive oxygen species （ROS） and osteopontin （OPN） in renal tissue of rats were determined； mRNA and protein expressions of SIRT3， FOXO3a， and SOD2 in renal tissue of rats were determined. RESULTS Compared with blank group， 24 h urine volume， urine pH， SOD level， mRNA and protein expressions of SIRT3， FOXO3a and SOD2 in renal tissue were decreased significantly in model group （P＜0.05 or P＜0.01）. The contents of urine Ca2+ and Ox， serum contents of Cr， BUN and Ca2+ and the levels of ROS， MDA and OPN in renal tissue were increased significantly （P＜0.01）. The pathological damage of renal tissue was severe， with a large number of diffuse black crystals， thickened glomerular basement membrane， and mitochondrial edema in podocytes and renal tubular epithelial cells. Compared with model group， the above indexes （except for serum content of Ca2+ in low-dose group） were significantly reversed in Shilinqing granules groups （P＜0.05 or P＜0.01）； pathological renal damage， calcium crystal， mitochondrial damage of glomerular podocyte and renal tubular epithelial cell were significantly improved； there was no statistical significance in the changes of above indexes in SIRT3 inhibitor group （P＞0.05）. CONCLUSIONS Shilinqing granules can effectively inhibit the formation of calcium oxalate kidney stones in rats and improve renal damage， the mechanism of which may be related to the improvement of anti-oxidant effect and the activation of SIRT3/FOXO3a signaling pathway. |
| 期刊： | 2022年第33卷第23期 |
| 作者： | 靳潇潇，李卫胜，杨雄，郑聪，何文强 |
| AUTHORS： | JIN Xiaoxiao，LI Weisheng，YANG Xiong，ZHENG Cong，HE Wenqiang |
| 关键字： | 石淋清颗粒；草酸钙；肾结石；肾损伤；抗氧化；SIRT3/FOXO3a信号通路 |
| KEYWORDS： | Shilinqing granules； calcium oxalate； kidney stones； renal damage； anti-oxidant； SIRT3/FOXO3a signaling |
| 阅读数： | 221 次 |
| 本月下载数： | 3 次 |
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