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落新妇苷对慢性肾功能衰竭大鼠肾损伤的影响及机制
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| 篇名： | 落新妇苷对慢性肾功能衰竭大鼠肾损伤的影响及机制 |
| TITLE： | Effects and mechanism of astilbin on renal injury in chronic renal failure rats |
| 摘要： | 目的 基于Jagged-1/Notch-1信号通路探讨落新妇苷（AST）对慢性肾功能衰竭（CRF）大鼠肾损伤的影响及潜在机制。方法以5/6肾切除术法构建CRF模型，并将造模成功的大鼠随机分为模型组（Model组）、AST低剂量组（AST-L组）、AST高剂量组（AST-H组）、AST高剂量+Notch通路激活剂（Jagged1/FC嵌合蛋白，简称“JFC”）组（AST-H+JFC组），另设开腹不切除的对照组（CK组），每组10只。AST-L组和AST-H组大鼠分别灌胃40、80mg/kg的AST，AST-H+JFC组大鼠同时灌胃80mg/kg的AST和0.5mg/kg的JFC，CK组和Model组大鼠灌胃等体积生理盐水，每天1次，连续4周。末次给药后，检测各组大鼠血清尿素氮（BUN）、血清肌酐（SCr）、24h尿液尿蛋白（UP）水平以及血清乳酸脱氢酶（LDH）、肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、IL-10水平；观察其肾组织形态和纤维化情况，检测肾组织线粒体中腺苷三磷酸（ATP）含量和钠钾ATP酶、钙镁ATP酶活性，以及肾组织中转化生长因子β（TGF-β）、低氧诱导因子1α（HIF-1α）、α-平滑肌肌动蛋白（α-SMA）、切割型胱天蛋白酶3（cleaved-caspase-3）、Jagged-1、Notch-1蛋白的表达水平。结果与CK组比较，Model组大鼠肾组织损伤明显，肾组织纤维化严重；其血清BUN、SCr和尿液UP水平，血清LDH、TNF-α、IL-6水平，以及肾组织中TGF-β、HIF-1α、α-SMA、cleaved-caspase-3、Jagged-1、Notch-1蛋白的表达水平均显著升高，血清IL-10水平以及肾组织线粒体中ATP含量和钠钾ATP酶、钙镁ATP酶活性均显著降低（P＜0.05）。与Model组比较，AST各剂量组大鼠肾组织损伤和纤维化均有所减轻；其血清BUN、SCr和尿液UP水平，血清LDH、TNF-α、IL-6水平，以及肾组织中TGF-β、HIF-1α、α-SMA、cleaved-caspase-3、Jagged-1、Notch-1蛋白的表达水平均显著降低，血清IL-10水平以及肾组织线粒体中ATP含量和钠钾ATP酶、钙镁ATP酶活性均显著升高，且AST-H组上述指标的变化较AST-L组明显（P＜0.05）。JFC可显著逆转高剂量AST对CRF大鼠肾损伤的改善作用（P＜0.05）。结论AST可减轻CRF大鼠炎症、肾组织损伤和纤维化，改善肾组织线粒体能量代谢，上述作用可能与抑制Jagged-1/Notch-1信号通路有关。 |
| ABSTRACT： | OBJECTIVE To investigate the effect and potential mechanism of astilbin （AST） on renal injury in chronic renal failure （CRF） rats based on the Jagged-1/Notch-1 signaling pathway. METHODS CRF model was constructed by 5/6 nephrotomy. The successfully modeled rats were randomly separated into Model group， AST low-dose group （AST-L group）， AST high-dose group （AST-H group）， high-dose of AST+Notch pathway activator （Jagged-1/FC chimerin， referred to as “JFC”） group （AST-H+ JFC group）， and control group （CK group） for open surgery without resection was set up， with 10 rats in each group. The rats in the AST-L group and AST-H group were given 40 and 80 mg/kg AST， respectively； the rats in the AST-H+JFC group were simultaneously given 80 mg/kg AST and 0.5 mg/kg JFC， and the rats in the CK group and Model group were given an equal volume of normal saline， once a day， for 4 weeks. After the last administration， the serum levels of blood urea nitrogen （BUN）， serum creatinine （SCr）， and the level of 24 h urinary protein （UP） in urine， as well as the serum levels of lactate dehydrogenase （LDH）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-10 in each group were detected. The morphology and fibrosis of renal tissue were observed. The content of adenosine triphosphate （ATP） and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were detected. The protein expressions of transforming growth factor- β （TGF- β）， hypoxia-inducible factor-1α （HIF-1α）， α-smooth muscle actin （α-SMA）， cleaved-caspase-3， Jagged-1 and Notch-1 in renal tissue were also observed. RESULTS Compared with CK group， the renal tissue of rats in the Model group was obviously damaged， renal tissue fibrosis was severe； the serum BUN and SCr levels， urine UP level， serum 4 LDH， TNF-α and IL-6 levels， as well as the protein expressions of TGF-β， HIF-1α， α-SMA， cleaved-caspase-3， Jagged-1 and Notch-1 in renal tissue were significantly increased， while the serum IL-10 level， ATP content and activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were significantly decreased （P＜0.05）. Compared with Model group， the renal tissue damage and fibrosis in the AST groups were reduced， the serum BUN and SCr levels， urine UP level， serum LDH， TNF-α and IL-6 levels， and the protein expressions of TGF-β， HIF-1α， α-SMA， cleaved-caspase-3， Jagged-1 and Notch-1 were significantly decreased， while the serum IL-10 level， ATP content and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria were significantly increased； the changes in the aforementioned indicators in AST- H group were more significant than those in the AST-L group（P＜0.05）. JFC could significantly reverse the improvement effect of high dose of AST on renal injury in CRF rats （P＜0.05）. CONCLUSIONS AST can reduce inflammation in CRF rats， alleviate renal tissue damage and fibrosis， and improve renal mitochondrial capacity metabolism， possibly by inhibiting the Jagged-1/Notch-1 signaling pathway. |
| 期刊： | 2025年第36卷第04期 |
| 作者： | 高晓卫；刘迎迎；韩聪；郝世飞 |
| AUTHORS： | GAO Xiaowei，LIU Yingying，HAN Cong，HAO Shifei |
| 关键字： | 落新妇苷；慢性肾功能衰竭；肾损伤；肾纤维化；Jagged-1/Notch-1信号通路 |
| KEYWORDS： | astilbin； chronic renal failure； renal injury； renal fibrosis； Jagged-1/Notch-1 signaling pathway |
| 阅读数： | 5 次 |
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