Zhang S, Su B, Wang L, Tang S, Chen G
Department of Nephrology, Frist Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2022 Dec 20;42(12):1852-1857. doi: 10.12122/j.issn.1673-4254.2022.12.14.
To investigate the effect of tanshinone IIA pretreatment on acute renal injury in lipopolysaccharide (LPS)-induced septic mice and explore the possible mechanism.
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 p-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 p-FUNDC1, and qRT-PCR was used to detect the expression of RIP3 mRNA.
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 p-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 p-FUNDC1 proteins. In HK-2 cells, LPS stimulation significantly increased the protein expressions of RIP3, cleaved caspase-3 and p-FUNDC1 and induced obvious cell apoptosis. Pretreatment with tanshinone IIA strongly inhibited the expression of RIP3 and p-FUNDC1 and reduced LPS-induced apoptosis of HK-2 cells.
Tanshinone IIA can reduce LPS-induced apoptosis of renal tubular epithelial cells by inhibiting RIP3/FUNDC1 signal pathway.
探讨丹参酮IIA预处理对脂多糖（LPS）诱导的脓毒症小鼠急性肾损伤的影响，并探究其可能机制。
将30只C57BL/6小鼠随机分为生理盐水处理组（对照组）、10mg/kg LPS处理24小时组或LPS处理前15分钟给予10mg/kg丹参酮IIA组。处理后，检测小鼠血清肌酐和血尿素氮水平，用PAS染色观察肾脏病理变化，用蛋白质印迹法检测肾脏中RIP3、裂解的半胱天冬酶-3和p-FUNDC1的表达。在细胞实验中，用LPS（10mg/mL）、LPS+siNC、LPS+siRIP3或LPS+丹参酮IIA（10mg/L）处理培养的正常人肾小管上皮细胞（HK-2），用TUNEL染色检测细胞凋亡变化；用蛋白质印迹法检测RIP3、裂解的半胱天冬酶-3和p-FUNDC1的表达水平，用qRT-PCR检测RIP3 mRNA的表达。
LPS攻击24小时显著升高小鼠血清肌酐和血尿素氮水平，导致近端肾小管明显损伤，并增加肾脏中RIP3、裂解的半胱天冬酶-3和p-FUNDC1蛋白的表达。丹参酮IIA预处理显著改善LPS诱导的小鼠肾损伤，减轻肾细胞凋亡，并抑制RIP3、裂解的半胱天冬酶-3和p-FUNDC1蛋白的表达。在HK-2细胞中，LPS刺激显著增加RIP3、裂解的半胱天冬酶-3和p-FUNDC1的蛋白表达并诱导明显的细胞凋亡。丹参酮IIA预处理强烈抑制RIP3和p-FUNDC1的表达并减少LPS诱导的HK-2细胞凋亡。
丹参酮IIA可通过抑制RIP3/FUNDC1信号通路减轻LPS诱导的肾小管上皮细胞凋亡。
