| 丹参酮IIA通过抑制RIP3/FUNDC1信号通路减轻LPS诱导的小鼠肾小管上皮细胞凋亡 |
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| 引用本文： | 张 舒,苏保林,王亮亮,汤水福,陈刚毅.丹参酮IIA通过抑制RIP3/FUNDC1信号通路减轻LPS诱导的小鼠肾小管上皮细胞凋亡[J].南方医科大学学报,2022,42(12):1852-1857. |
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| 作者姓名： | 张 舒 苏保林 王亮亮 汤水福 陈刚毅 |
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| 作者单位： | 广州中医药大学第一附属医院肾病科，广东 广州 510405 |
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| 摘 要： | 目的 探讨丹参酮IIA在防治脓毒血症急性肾损伤（AKI）方面的作用及潜在机制。方法 将30只C57BL/6小鼠随机分为对照组（10 mg/kg LPS等体积无菌生理盐水）、LPS组（10 mg/kg LPS作用24 h）、LPS+丹参酮IIA组（10 mg/kg 丹参酮IIA预处理15 min再给予10 mg/kg LPS作用24 h）（10只/组）。给药后检测小鼠血肌酐(Scr)、血尿素氮水平(BUN)，PAS染色观察小鼠肾组织病理变化，Western blot检测小鼠肾组织RIP3、Cleaved-caspase3、p18-FUNDC1表达水平。将体外培养正常的人肾小管上皮细胞（HK-2）分为空白对照组、LPS 刺激组（LPS，10 μg/mL）、LPS+siNC 组（LPS 10 μg/mL+50 nmol/L siNC）、LPS+siRIP3 组（LPS 10 μg/mL+50 nmol/L siRIP3）、丹参酮IIA干预组（LPS 10 μg/mL+ 丹参酮IIA 10 mg/L），分别给予以上干预措施。采用TUNEL方法检测各组HK-2细胞的凋亡情况，Western blot检测各组RIP3、Cleaved-caspase3、p18-FUNDC1表达水平，qT-PCR检测RIP3基因表达水平。结果 与对照组相比，LPS作用小鼠24 h后，小鼠Scr及血BUN水平升高，PAS染色提示近段肾小管损伤，肾组织中RIP3、Cleaved-caspase3、p18-FUNDC1蛋白表达上调（P<0.001）。与LPS组相比，丹参酮IIA预处理后，小鼠Scr及BUN水平下降，PAS染色显示近段肾小管损伤减轻，肾组织中RIP3、Cleaved-caspase3、p18- FUNDC1蛋白表达下降（P<0.001）。体外研究显示，与对照组相比，LPS刺激的HK-2细胞后，TUNEL染色显示细胞凋亡水平明显增加，Cleaved-caspase3、RIP3、p18-FUNDC1表达上调（P<0.05）。应用丹参酮IIA预处理或体外沉默RIP3表达后再次予以LPS刺激细胞，TUNEL染色显示细胞凋亡水平较LPS组明显减少，Cleaved-caspase3、RIP3、p18-FUNDC1表达水平较LPS组下降（P<0.05）。结论 丹参酮IIA可能通过抑制RIP3/ FUNDC1信号通路来改善LPS诱导的肾小管上皮细胞凋亡。
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| 关 键 词： | 丹参酮IIA 急性肾损伤 受体相关蛋白-3 细胞凋亡 FUN14结构域蛋白1 |
Tanshinone IIA alleviates lipopolysaccharide-induced renal tubular epithelial cell apoptosis by inhibiting RIP3/FUNDC1 signaling pathway |
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| ZHANG Shu,SU Baolin,WANG Liangliang,TANG Shuifu,CHEN Gangyi.Tanshinone IIA alleviates lipopolysaccharide-induced renal tubular epithelial cell apoptosis by inhibiting RIP3/FUNDC1 signaling pathway[J].Journal of Southern Medical University,2022,42(12):1852-1857. |
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| Authors: | ZHANG Shu SU Baolin WANG Liangliang TANG Shuifu CHEN Gangyi |
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| Affiliation: | Department of Nephrology, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China |
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| Abstract: | Objective To investigate the effect of tanshinone IIA pretreatment on acute renal injury in lipopolysaccharide (LPS)-induced septic mice and explore the possible mechanism. Methods Thirty C57BL/6 mice were randomized for treatment with saline (control), 10 mg/kg LPS for 24 h, or 10 mg/kg tanshinone IIA 15 min before LPS treatment. After the treatments, serum creatinine and blood urea nitrogen levels of the mice were detected, renal pathologies were observed with PAS staining, and renal expressions of RIP3, cleaved caspase- 3 and p18- FUNDC1 were detected with Western blotting. In the cell experiment, cultured normal human renal tubular epithelial cells (HK-2) were treated with LPS (10 mg/mL), LPS + siNC, LPS + siRIP3, or LPS+tanshinone IIA (10 mg/L), and the changes in cell apoptosis were examined with TUNEL staining; Western blotting was performed to detect the expression levels of RIP3, cleaved caspase-3 and p18-FUNDC1, and qRT-PCR was used to detect the expression of RIP3 mRNA. Results LPS challenge for 24 h significantly increased serum creatinine and blood urea nitrogen levels in the mice, caused obviously damages in the proximal renal tubules, and increased renal expressions of RIP3, cleaved caspase-3 and p18-FUNDC1 proteins. Tanshinone IIA pretreatment significantly improved LPS-induced renal injury in the mice, alleviated apoptosis of the renal cells, and inhibited the expressions of RIP3, cleaved caspase-3 and p18-FUNDC1 proteins. In HK-2 cells, LPS stimulation significantly increased the protein expressions of RIP3, cleaved caspase-3 and p18-FUNDC1 and induced obvious cell apoptosis. Pretreatment with tanshinone IIA strongly inhibited the expression of RIP3 and p18-FUNDC1 and reduced LPS-induced apoptosis of HK- 2 cells. Conclusion Tanshinone IIA can reduce LPS-induced apoptosis of renal tubular epithelial cells by inhibiting RIP3/FUNDC1 signal pathway. |
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| Keywords: | tanshinone IIA acute renal injury receptor-interacting protein kinase 3 apoptosis FUN14 domain-containing protein 1 |
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