| 康 博,惠鹏宇,郭高英,王 钧,苏雯静.三七总皂苷联合顺铂对胃癌大鼠肾损伤的改善作用及机制分析[J].现代生物医学进展英文版,2023,(11):2030-2034. |
| 三七总皂苷联合顺铂对胃癌大鼠肾损伤的改善作用及机制分析 |
| Effect and Mechanism of Panax Notoginseng Saponins Combined with Cisplatin on Renal injury in Rats with Gastric Cancer |
| Received:November 25, 2022 Revised:December 21, 2022 |
| DOI：10.13241/j.cnki.pmb.2023.11.006 |
| 中文关键词: 三七皂苷 胃癌 顺铂 肾损伤 机制 |
| 英文关键词: Panax notoginseng saponins Gastric cancer Cisplatin Renal injury Mechanism |
| 基金项目:陕西省教育厅科研项目（20JK0894） |
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| 中文摘要: |
| 摘要 目的：探讨三七总皂苷联合顺铂对胃癌大鼠肾损伤的改善作用并分析潜在机制。方法：选择60只健康SD雄性大鼠分为对照组、胃癌模型组、顺铂组及三七总皂苷组，各15只。除对照组外，其余组大鼠采用皮下接种胃癌BGC823细胞悬液法建立胃癌模型。建模成功后，给予对照组和胃癌模型组大鼠生理盐水腹腔注射和灌胃，给予顺铂组大鼠腹腔注射25 mg/kg顺铂注射液并灌胃生理盐水，给予三七总皂苷组大鼠腹腔注射25 mg/kg顺铂注射液并灌胃30 mg/kg三七总皂苷。分别于建模成功时、药物处理28 d时采用酶联免疫吸附法检测血清肌酐（SCr）、尿素氮（BUN）和尿液β-N-乙酰氨基葡萄糖苷酶（NAG）、肾损伤分子1（KIM-1）水平。处死大鼠后取肾脏，分别测定肾脏组织匀浆中超氧化物歧化酶（SOD）、丙二醛（MDA）、过氧化氢酶（CAT）、谷胱甘肽（GSH）水平，制备肾脏组织石蜡切片并行苏木精-伊红染色后观察大鼠肾组织的病理学变化。采用TUNEL染色法检测肾脏组织细胞凋亡情况，采用Western Blotting法检测肾脏组织中LC3、HIF-1α和Beclin1 蛋白表达情况。结果：顺铂组和三七总皂苷组大鼠血清SCr、BUN和尿液NAG、KIM-1水平均显著高于对照组和模型组（P<0.05），三七总皂苷组大鼠血清SCr、BUN和尿液NAG、KIM-1水平显著高于顺铂组（P<0.05）。三七总皂苷组大鼠肾脏组织SOD、GSH水平显著低于模型组但显著高于顺铂组，MDA显著高于模型组但显著低于顺铂组（P＜0.05），CAT与模型组无显著差异（P＜0.05），但显著高于顺铂组（P>0.05）。顺铂组大鼠肾小管明显扩张、管腔狭窄，基底层上皮细胞水肿、坏死并形成空泡，肾小管。三七总皂苷组大鼠肾脏病理学改变程度显著轻于顺铂组。顺铂组和三七总皂苷组大鼠肾脏组织细胞凋亡指数显著增加，三七总皂苷组大鼠肾脏组织细胞凋亡指数显著低于顺铂组（P＜0.05）。顺铂组大鼠肾脏组织中LC3、HIF-1α和Beclin1蛋白水平均显著高于模型组，但显著低于三七总皂苷组（P＜0.05）。结论：三七总皂苷可能通过减轻过氧自由基和过氧化水平、增强线粒体自噬水平减少肾组织细胞凋亡，减轻顺铂引起的胃癌大鼠肾损伤。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of panax notoginseng saponins combined with cisplatin on renal injury in rats with gastric cancer and analyze the potential mechanism. Methods: 60 healthy male SD rats were divided into control group, gastric cancer model group, cisplatin group and panax notoginseng saponins group with 15 rats each. Except the control group, gastric cancer models were established by subcutaneous inoculation of gastric cancer BGC823 cell suspension in other groups. After successful modeling, rats in the control group and gastric cancer model group were given intraperitoneal injection and gastric perfusion of normal saline, rats in the cisplatin group were given intraperitoneal injection of 25 mg/kg cisplatin and gastric perfusion of normal saline, and rats in the panax notoginseng saponins group were given intraperitoneal injection of 25 mg/kg cisplatin and gastric perfusion of 30 mg/kg panax notoginseng saponins. Serum creatinine(SCR), urea nitrogen(BUN) and urine β-N-acetylglucosaminidase(NAG) and kidney injury molecule 1 (KIM-1) levels were detected by enzyme-linked immunosorbent assay at the time of successful modeling and 28 days after drug treatment, respectively. After the rats were killed, the kidneys were taken, and the levels of superoxide dismutase(SOD), malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) in the renal tissue homogenate were measured respectively. The paraffin sections of kidney tissue were prepared and hematoxylin eosin staining was used to observe the pathological changes of the kidney tissue. TUNEL staining was used to detect apoptosis in renal tissue, and Western Blotting was used to detect LC3 and HIF-1α and Beclin1 protein expression in renal tissue. Results: The levels of serum SCR, BUN and urine NAG, KIM-1 in rats of cisplatin group and panax notoginseng saponin group were higher than those of control group and model group(P<0.05), and the levels of serum SCR, BUN, urine NAG, KIM-1 in rats of panax notoginseng saponin group were higher than those of cisplatin group (P<0.05). The levels of SOD and GSH in kidney tissue of rats in panax notoginseng saponins group were lower than those in the model group but significantly higher than those in the cisplatin group, MDA was significantly higher than those in the model group but lower than those in the cisplatin group(P<0.05), CAT had no difference from the model group(P<0.05), but higher than those in the cisplatin group(P>0.05). In the cisplatin group, the renal tubules were obviously expanded, the lumen was narrowed, and the epithelial cells in the basal layer were edematous, necrotic and formed vacuoles. The pathological changes of kidney in panax notoginseng saponins group were lighter than those in cisplatin group. The apoptosis index of renal tissue cells in cisplatin group and panax notoginseng saponins group was increased, while that in panax notoginseng saponins group was lower than that in cisplatin group(P<0.05). LC3 and HIF-1α and Beclin1 protein levels in kidney tissue of rats in cisplatin group were higher than those in the model group, but lower than those in the panax notoginseng saponins group (P<0.05). Conclusion: Panax notoginseng saponins may reduce the apoptosis of renal tissue cells by reducing the level of peroxy free radicals and peroxides, affecting the HIF-1α pathway to enhance the level of mitochondrial autophagy, and alleviate the renal injury of rats with gastric cancer caused by cisplatin. |
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