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一种中药复方通过抗凋亡和抗炎作用减轻顺铂诱导的小鼠急性肾损伤

A Chinese Medicine Compound Alleviates Cisplatin-Induced Acute Kidney Injury via Its Antiapoptosis and Anti-Inflammation Effects in Mice.

作者信息

He Riming, Liu Jiahui, Chen Yulian, Liao Yijiao, Wang Yuzhi, Jin Xiaoming, Li Zhongtang, Liu Siqi, Lu Jiandong, Yang Shudong

机构信息

Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.

Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, Guangdong, China.

出版信息

Evid Based Complement Alternat Med. 2022 Jun 29;2022:7841284. doi: 10.1155/2022/7841284. eCollection 2022.

Abstract

Cisplatin, also known as cis-diamine dichloroplatinum (CDDP), is a widely used chemotherapeutic drug. However, its application is limited by the occurrence of serious nephrotoxicity. Currently, no effective therapy is available for combating CDDP-induced acute kidney injury (AKI). In the present study, we investigated the efficacy of Jianpi Yishen Tang (JPYST), a traditional Chinese medicine (TCM) compound commonly used to treat chronic kidney disease, against CDDP-induced AKI. In the CDDP + JPYST group, male mice were pretreated with JPYST (18.35 g/kg/day) for 5 consecutive days before receiving a single dose of CDDP (20 mg/kg), all mice were sacrificed 72 h after the CDDP injection. Results showed that JPYST suppressed CDDP-induced kidney dysfunction and tubular damage scores in the mice. Mechanistically, JPYST treatment attenuated CDDP-induced renal tubular cell apoptosis in AKI mice, as manifested by a marked decreased in TUNEL-positive cell counts, downregulation of the pro-apoptotic proteins Bax, Bad and caspase 3, and upregulation of the antiapoptotic protein Bcl-2 in kidney tissues. Meanwhile, JPYST decreased the expression of inflammatory cytokines TNF-, IL-1, and IL-6 in the serum and renal tissues of mice following CDDP administration. These factors are involved in suppressing the activation of phospho-NF-B p65 in tubular epithelial cells. Taken together, these findings demonstrated that JPYST exerts renoprotective effects against CDDP-induced AKI through antiapoptosis and anti-inflammation effects, and these are associated with downregulation of NF-B activation. Therefore, JPYST has potential for development of treatment therapies against CDDP-induced AKI.

摘要

顺铂,也称为顺二氨二氯铂(CDDP),是一种广泛使用的化疗药物。然而,其应用受到严重肾毒性发生的限制。目前,尚无有效的疗法来对抗顺铂诱导的急性肾损伤(AKI)。在本研究中,我们研究了健脾益肾汤(JPYST),一种常用于治疗慢性肾病的中药复方,对顺铂诱导的AKI的疗效。在顺铂+健脾益肾汤组中,雄性小鼠在接受单剂量顺铂(20mg/kg)之前,连续5天用健脾益肾汤(18.35g/kg/天)进行预处理,所有小鼠在顺铂注射后72小时处死。结果表明,健脾益肾汤抑制了顺铂诱导的小鼠肾功能障碍和肾小管损伤评分。机制上,健脾益肾汤治疗减轻了顺铂诱导的急性肾损伤小鼠肾小管细胞凋亡,表现为肾组织中TUNEL阳性细胞计数显著减少、促凋亡蛋白Bax、Bad和半胱天冬酶3下调以及抗凋亡蛋白Bcl-2上调。同时,健脾益肾汤降低了顺铂给药后小鼠血清和肾组织中炎性细胞因子TNF-、IL-1和IL-6的表达。这些因素参与抑制肾小管上皮细胞中磷酸化NF-κB p65的激活。综上所述,这些发现表明健脾益肾汤通过抗凋亡和抗炎作用对顺铂诱导的急性肾损伤发挥肾保护作用,且这些作用与NF-κB激活的下调有关。因此,健脾益肾汤具有开发治疗顺铂诱导的急性肾损伤治疗方法的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a51/9259212/07979c7b115c/ECAM2022-7841284.001.jpg

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