Liang Taolin, Wei Chongying, Lu Sisi, Qin Mengyuan, Qin Guiming, Zhang Yansong, Zhong Xiaobin, Zou Xiaoqin, Yang Yufang
Postgraduate Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Regenerative Medicine Research Center of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Biomed Rep. 2021 Apr;14(4):38. doi: 10.3892/br.2021.1414. Epub 2021 Feb 26.
Ginaton injection (Ginkgo biloba extract; GBE) has been reported to protect against cisplatin-induced acute renal failure in rats. In the present study, the effects and molecular mechanisms of GBE on cisplatin-induced renal interstitial fibrosis were evaluated using a rat model. The rats were intraperitoneally injected with cisplatin once on the first day and a subset of rats were treated with GBE or SB203580 (SB; a specific p38 MAPK inhibitor) daily from days 22 to 40. The levels of N-acetyl-β-D-Glucosaminidase (NAG) in the urine, and of urea nitrogen (BUN) and creatinine (Scr) in the blood were assessed. The damage and fibrosis of renal tissues were evaluated using hematoxylin and eosin staining, as well as Masson's trichrome staining, respectively. Apoptosis in renal tissues was detected using a TUNEL assay. The protein expression levels of α-smooth muscle actin (SMA), collagen 1 (Col I), Bax, Bcl-2, caspase-3/cleaved caspase-3, hypoxia-inducible factor-1α (HIF-1α), TGF-β1 and p38MAPK, as well as the mRNA levels of p38MAPK in renal tissues were investigated. The results showed that GBE markedly reduced the levels of urinary NAG, Scr and BUN, and renal expression of α-SMA and Col I levels were also reduced. Furthermore, GBE significantly reduced renal tissue injury and the relative area of renal interstitial fibrosis induced by cisplatin. GBE effectively reduced the apoptotic rate of renal tissues, the protein expression levels of Bax, cleaved caspase-3, phospho-p38MAPK, TGF-β1 and HIF-1α, as well as the mRNA expression levels of p38MAPK in renal tissues induced by cisplatin, whereas GBE significantly increased Bcl-2 protein expression. SB exhibited similar effects to GBE, although it was not as effective. In summary, the present study is the first to show that GBE significantly alleviated renal interstitial fibrosis following cisplatin-induced acute renal injury. The mechanisms by which GBE exhibited its effects were associated with the inhibition of apoptosis via downregulation of the p38MAPK/TGF-β1 and p38MAPK/HIF-1α signaling pathways.
已报道金纳多注射液（银杏叶提取物；GBE）可保护大鼠免受顺铂诱导的急性肾衰竭。在本研究中，使用大鼠模型评估了GBE对顺铂诱导的肾间质纤维化的影响及其分子机制。大鼠在第一天腹腔注射一次顺铂，从第22天至第40天，一部分大鼠每天接受GBE或SB203580（SB；一种特异性p38丝裂原活化蛋白激酶抑制剂）治疗。评估了尿液中N-乙酰-β-D-葡萄糖苷酶（NAG）水平以及血液中尿素氮（BUN）和肌酐（Scr）水平。分别使用苏木精-伊红染色以及Masson三色染色评估肾组织的损伤和纤维化。使用TUNEL检测法检测肾组织中的细胞凋亡。研究了肾组织中α-平滑肌肌动蛋白（SMA）、胶原蛋白1（Col I）、Bax、Bcl-2、半胱天冬酶-3/裂解的半胱天冬酶-3、缺氧诱导因子-1α（HIF-1α）、转化生长因子-β1（TGF-β1）和p38丝裂原活化蛋白激酶（p38MAPK）的蛋白表达水平，以及肾组织中p38MAPK的mRNA水平。结果表明，GBE显著降低了尿NAG、Scr和BUN水平，肾组织中α-SMA和Col I的表达水平也降低。此外，GBE显著减轻了顺铂诱导的肾组织损伤和肾间质纤维化的相对面积。GBE有效降低了顺铂诱导的肾组织凋亡率、肾组织中Bax、裂解的半胱天冬酶-3、磷酸化p38MAPK、TGF-β1和HIF-1α的蛋白表达水平以及p38MAPK的mRNA表达水平，而GBE显著增加了Bcl-2蛋白表达。SB表现出与GBE相似的作用，尽管效果不如GBE。总之，本研究首次表明GBE可显著减轻顺铂诱导急性肾损伤后的肾间质纤维化。GBE发挥作用的机制与通过下调p38MAPK/TGF-β1和p38MAPK/HIF-1α信号通路抑制细胞凋亡有关。
