Xie Jing, Ma Xin, Li Xueying, Mao Nan, Ren Sichong, Fan Junming
Yubei District people's Hospital of Chongqing, Chongqing 401320, China.
Chengdu University of Traditional Chinese Medicine, Chengdu 610032, China.
Curr Pharm Biotechnol. 2023 Apr 17. doi: 10.2174/1389201024666230417084507.
Renal fibrosis is related to impaired kidney function and can eventually lead to end-stage renal disease, for which no effective treatment is available. Panax notoginseng saponins (PNS), as a commonly used traditional Chinese medicine, is considered a possible alternative for the treatment of fibrosis.
The purpose of the present study was to investigate the effects and possible mechanisms of PNS on renal fibrosis.
HK-2 cells were used to induce renal fibrosis cell model by lipopolysaccharide (LPS), and the cytotoxicity of PNS on HK-2 cells was investigated. Cell damage, pyroptosis, and fibrosis were analyzed to investigate the effects of PNS on LPS-induced HK-2 cells. NLRP3 agonist Nigericin was used further to explore the inhibitory effect of PNS on LPS-induced pyroptosis so as to clarify the possible mechanism of PNS on renal fibrosis.
PNS had no cytotoxicity on HK-2 cells, and could reduce the apoptosis and the release of lactate dehydrogenase (LDH) and inflammatory cytokines of LPS-induced HK-2 cells, showing an alleviating effect on cell damage. PNS also reduced the expression of pyroptosis proteins NLRP3, IL-1β, IL-18, and Caspase-1, as well as fibrosis proteins α-SMA, collagen Ⅰ and p-Smad3/Smad3, which showed an inhibitory effect on LPS-induced pyroptosis and fibrosis. In addition, LPS-induced cell damage, pyroptosis, and fibrosis were aggravated after Nigericin treatment, while PNS alleviated the aggravation caused by Nigericin.
PNS inhibits pyroptosis by inhibiting the activation of NLRP3 inflammasome in LPS-induced HK-2 cells, which ultimately alleviates renal fibrosis and plays a good role in the treatment of kidney diseases.
肾纤维化与肾功能受损有关，最终可导致终末期肾病，目前尚无有效的治疗方法。三七总皂苷（PNS）作为一种常用的传统中药，被认为是治疗纤维化的一种可能替代药物。
本研究旨在探讨PNS对肾纤维化的影响及可能机制。
采用脂多糖（LPS）诱导HK-2细胞建立肾纤维化细胞模型，研究PNS对HK-2细胞的细胞毒性。分析细胞损伤、焦亡和纤维化情况，以研究PNS对LPS诱导的HK-2细胞的影响。进一步使用NLRP3激动剂尼日利亚菌素探讨PNS对LPS诱导的焦亡的抑制作用，以阐明PNS对肾纤维化的可能机制。
PNS对HK-2细胞无细胞毒性，可减少LPS诱导的HK-2细胞凋亡、乳酸脱氢酶（LDH）释放及炎性细胞因子分泌，对细胞损伤有减轻作用。PNS还降低了焦亡蛋白NLRP3、白细胞介素-1β（IL-1β）、白细胞介素-18（IL-18）和半胱天冬酶-1（Caspase-1）以及纤维化蛋白α-平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原和磷酸化Smad3/ Smad3的表达，对LPS诱导的焦亡和纤维化有抑制作用。此外，尼日利亚菌素处理后LPS诱导的细胞损伤、焦亡和纤维化加重，而PNS减轻了尼日利亚菌素引起的加重。
PNS通过抑制LPS诱导的HK-2细胞中NLRP3炎性小体的激活来抑制焦亡，最终减轻肾纤维化，对肾脏疾病治疗具有良好作用。
