Jinan University, Guangzhou 510632, China; Institute of Biomineralization and Lithiasis Research, College of Chemistry and Materials Science, Guangzhou 510632, China.
Jinan University, Guangzhou 510632, China; Institute of Biomineralization and Lithiasis Research, College of Chemistry and Materials Science, Guangzhou 510632, China.
Biomed Pharmacother. 2023 Dec 31;169:115865. doi: 10.1016/j.biopha.2023.115865. Epub 2023 Nov 14.
The inhibitory effects of Chinese medicine Pocoa (PCPs) with different carboxyl group (-COOH) contents on oxidative damage and inflammatory response of renal epithelial cells and the influence of -COOH content in polysaccharides were investigated. HK-2 cell damage model was established by nanocalcium oxalate crystals (nanoCOM), and then PCPs with -COOH contents of 2.56% (PCP0), 7.48% (PCP1), 12.07% (PCP2), and 17.18% (PCP3) were used to protect the cells. PCPs could inhibit the damage of nanoCOM to HK-2 cells, increase cell viability, restore cytoskeleton and morphology, and improve lysosomal integrity. PCPs can reduce the oxidative stress response of nanoCOM to cells, inhibit the opening of mPTP and cell necrotic apoptosis, reduce the level of Ca ions in cells, the production of ATP and MDA, and increase SOD expression. PCPs can also reduce the cellular inflammatory response caused by oxidative damage, and reduce the expression of nitric oxide (NO), inflammatory factors TNF-α, IL-6, IL-1β and MCP-1, as well as the content of inflammasome NLRP3. After protection, PCPs can inhibit the endocytosis of nanoCOM crystals by cells. With the increase in -COOH content in PCPs, its ability to inhibit nanoCOM cell damage, reduce oxidative stress, reduce inflammatory response, and inhibit crystal endocytosis increases, that is, PCP3 with the highest -COOH content, shows the best biological activity. Inhibiting cell damage and inflammation and reducing a large amount of endocytosis of crystals by cells are beneficial to inhibit the formation of kidney stones.
研究了不同羧基（-COOH）含量的中药 Pocoa（PCPs）对肾上皮细胞氧化损伤和炎症反应的抑制作用，以及多糖中-COOH 含量的影响。通过纳米草酸钙晶体（nanoCOM）建立 HK-2 细胞损伤模型，然后用羧基含量为 2.56%（PCP0）、7.48%（PCP1）、12.07%（PCP2）和 17.18%（PCP3）的 PCPs 保护细胞。PCPs 可抑制 nanoCOM 对 HK-2 细胞的损伤，提高细胞活力，恢复细胞骨架和形态，改善溶酶体完整性。PCPs 可降低 nanoCOM 对细胞的氧化应激反应，抑制 mPTP 开放和细胞坏死凋亡，降低细胞内 Ca 离子、ATP 和 MDA 水平，增加 SOD 表达。PCPs 还可以降低氧化损伤引起的细胞炎症反应，降低一氧化氮（NO）、炎症因子 TNF-α、IL-6、IL-1β和 MCP-1的表达，以及炎症小体 NLRP3 的含量。保护后，PCPs 可抑制细胞对 nanoCOM 晶体的内吞作用。随着 PCPs 中-COOH 含量的增加，其抑制 nanoCOM 细胞损伤、降低氧化应激、降低炎症反应和抑制晶体内吞的能力增加，即羧基含量最高的 PCP3 表现出最佳的生物学活性。抑制细胞损伤和炎症反应，减少细胞对大量晶体的内吞作用，有利于抑制肾结石的形成。
