恶病质是一种多因素综合征，是癌症患者常见的后遗症。根据肿瘤阶段的不同，该比例从 42% 到 80% 不等，并且直接导致这些患者 30% 的死亡。我们实验室之前的研究表明，NSG 小鼠中产生的腹膜卵巢癌会导致骨骼肌和心肌萎缩，从而导致骨骼肌质量和强度丧失以及心脏功能障碍（恶病质）。腹腔注射小鼠的治疗醉茄素 A (WFA) 治疗的肿瘤显示出骨骼肌和心脏恶病质的逆转。本研究的重点是确定腹膜卵巢肿瘤对肾脏损伤的影响以及 WFA 治疗对改善肾脏损伤的影响。我们通过向雌性 NSG 小鼠注射卵巢癌细胞系 (A2780) 产生腹膜内卵巢癌。注射癌细胞一周后，小鼠每三天接受一次 WFA（4 毫克/千克）治疗，持续三周。注射癌细胞4周后，处死小鼠，收集包括肾脏和血液在内的各种组织，在液氮中速冻，并保存在-800℃下。通过 ELISA 测量血浆中肾脏生物标志物肌酐的存在。从小鼠肾脏中分离出 mRNA，用于检查信号蛋白、炎症细胞因子和导致恶病质的基因（IL-1β、IL-6、TNF-α、TGF-β、GDF-15 和MYD88)。我们的结果显示炎症细胞因子 IL-1 β (p < 0.01)、IL-6 (p < 0.001)、TNF-α (p < 0.001) 和其他相关基因（包括 TRAF6）的表达水平显着增加与对照组相比，荷瘤小鼠中的 (p< 0.01)、MYD88 (p< 0.01) 和 GDF-15 (p = 0.005)。用 WFA 治疗荷瘤小鼠可减弱每种基因表达的增加。此外，我们的结果显示，与对照小鼠相比，荷瘤小鼠的循环肌酐水平显着增加。与荷瘤小鼠相比，用 WFA 治疗荷瘤小鼠的血浆肌酐水平显着降低。我们的结果得出结论，NSG 小鼠的卵巢肿瘤引起肾损伤和肾功能障碍，而 WFA 治疗可有效改善这种情况，这表明WFA 对卵巢癌肾损伤的保护作用。© 2024。作者。

Cachexia a multifactorial syndrome is a common sequala in patients with cancer. It varies from 42 to 80% depending upon the oncological stage and is directly responsible for 30% of deaths in these patients. Previous research from our laboratory demonstrated that peritoneal ovarian cancer generated in NSG mice resulted in skeletal and cardiac muscle atrophy - leading to loss of skeletal muscle mass and strength, and cardiac dysfunction (cachexia). Treatment of mice bearing i.p. tumors with withaferin A (WFA) showed reversal of skeletal muscle and cardiac cachexia. The present study is focused on determining effects of peritoneal ovarian tumors on kidney damage and effects of WFA treatment on ameliorating kidney damage.We generated intraperitoneal ovarian cancer by injecting female NSG mice with ovarian cancer cell line (A2780). After one week of injecting cancer cells, mice were treated with WFA (4 mg/kg) every third day, for three weeks. After 4 weeks of injection of cancer cells, the mice were sacrificed and various tissues including kidney and blood were collected, snap-frozen in liquid nitrogen, and stored at -800C. The presence of kidney biomarker creatinine, was measured in the plasma by an ELISA. The mRNA was isolated from mouse kidneys and was used to examine the expression levels of signaling proteins, inflammatory cytokines, and genes responsible for inducing cachexia (IL-1β, IL-6, TNF-α, TGF-β, GDF-15, and MYD88).Our results showed a significant increase in levels of expression of inflammatory cytokine IL-1 β (p < 0.01), IL-6 (p < 0.001), TNF-α (p < 0.001), and other related genes including TRAF6 (p < 0.01), MYD88 (p < 0.01), and GDF-15 (p = 0.005) in tumor-bearing mice compared to controls. Treatment of mice bearing tumors with WFA attenuated the increase in expression of each gene. In addition, our results showed a significant increase in creatinine levels in circulation in tumor-bearing mice compared to control mice. Treatment of tumor-bearing mice with WFA resulted in a significant decrease in plasma creatinine levels compared to tumor-bearing mice.Our results conclude that ovarian tumors in NSG mice caused kidney damage and renal dysfunction, which was effectively ameliorated by WFA treatment, suggesting a protective effect of WFA on kidney injury induced by ovarian cancer.© 2024. The Author(s).