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1.遵义市第一人民医院肾脏内科,贵州 遵义 563000
2.遵义市第一人民医院风湿免疫科,贵州 遵义 563000
3.遵义市第一人民医院内分泌科,贵州 遵义 563000
副主任医师。研究方向:糖尿病肾病。E-mail:m15185282080_1@163.com
副主任医师,硕士。研究方向:糖尿病肾病、内分泌性高血压。E-mail:yangxiuyongwang@163.com
收稿:2025-12-18,
修回:2026-03-16,
录用:2026-03-16,
纸质出版:2026-04-15
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王永丽,陈海,田小芳,等.竹节参皂苷Ⅳa对糖尿病肾病大鼠的肾脏保护作用及机制 [J].中国药房,2026,37(07):908-913. DOI: 10.6039/j.issn.1001-0408.2026.07.14.
WANG Yongli,CHEN Hai,TIAN Xiaofang,et al.Protective effect and mechanism of chikusetsu saponin Ⅳa on the kidney in diabetic nephropathy rats[J].ZHONGGUO YAOFANG,2026,37(07):908-913. DOI: 10.6039/j.issn.1001-0408.2026.07.14.
王永丽,陈海,田小芳,等.竹节参皂苷Ⅳa对糖尿病肾病大鼠的肾脏保护作用及机制 [J].中国药房,2026,37(07):908-913. DOI: 10.6039/j.issn.1001-0408.2026.07.14. DOI:
WANG Yongli,CHEN Hai,TIAN Xiaofang,et al.Protective effect and mechanism of chikusetsu saponin Ⅳa on the kidney in diabetic nephropathy rats[J].ZHONGGUO YAOFANG,2026,37(07):908-913. DOI: 10.6039/j.issn.1001-0408.2026.07.14. DOI:
目的
2
研究竹节参皂苷Ⅳ
a
(chsⅣ)对糖尿病肾病(DN)模型大鼠肾脏功能的保护作用及可能机制。
方法
2
采用高脂饮食联合链脲佐菌素注射的方法构建DN大鼠模型。将造模成功的36只大鼠随机分为模型组(灌胃生理盐水,高脂饮食)和低、高剂量chsⅣ组(灌胃90、180 mg/kg chsⅣ,高脂饮食),每组12只;另取10只正常大鼠作为对照组(灌胃生理盐水,常规饮食)。自链脲佐菌素注射后的第5~12周,每天灌胃给药/生理盐水1次。末次给药后,测定大鼠空腹血糖、空腹胰岛素、血尿素氮、血肌酐、尿蛋白以及肾组织中还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和丙二醛(MDA)水平,计算胰岛素抵抗指数;采用苏木精-伊红、过碘酸希夫和Masson染色法观察肾组织病理学变化;采用免疫组化染色法与Western blot法检测肾组织中Notch信号通路相关蛋白的表达。
结果
2
与模型组比较,低、高剂量chsⅣ组大鼠的肾组织病理形态学均得到明显改善,肾脏组织学评分、系膜扩张指数以及肾小球硬化评分均显著降低(
P
<0.05),空腹血糖、空腹胰岛素、血尿素氮、血肌酐和尿蛋白水平,胰岛素抵抗指数,肾组织中MDA含量以及Notch1、Notch胞内结构域、毛状增强子分裂蛋白1和Delta样蛋白1的表达水平均显著降低(
P
<0.05),肾组织中GSH、SOD水平均显著升高(
P
<0.05),并且高剂量chsⅣ组大鼠的上述指标改善程度均显著优于低剂量chsⅣ组(
P
<0.05)。
结论
2
chsⅣ可改善DN大鼠的肾脏病理损伤及功能障碍,其潜在机制包括恢复血糖稳态与胰岛素敏感性、减轻肾组织氧化应激以及抑制Notch信号通路关键分子的异常激活。
OBJECTIVE
2
To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ
a
(chsⅣ) on renal function in diabetic nephropathy (DN) model rats.
METHODS
2
DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group (i.g. administration of normal saline, high-fat diet), chsⅣ low-dose and high-dose groups (i.g. administration of 90, 180 mg/kg chsⅣ, high-fat diet), with 12 rats in each group. Additionally, 10 normal rats were set as the control group (i.g. administration of normal saline, regular diet). From the 5th to the 12th week after streptozotocin injection, they were given intragastric administration of relevant drug or normal saline, once a day. After the last medication, the levels of fasting blood glucose, fasting insulin, blood urea nitrogen, serum creatinine and urine protein as well as the levels of reduced glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissues were measured. Additionally, the insulin resistance index was calculated. Hematoxylin-eosin, periodic acid-Schiff, and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods.
RESULTS
2
Compared with model group, the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved, with significant decreases in renal histological scores, mesangial expansion index, and glomerulosclerosis scores (
P
<0.05); the levels of fasting blood glucose, fasting insulin, blood urea nitrogen, serum creatinine, urine protein and homeostasis model assessment for insulin resistance, as well as MDA content, the expression levels of Notch1, Notch intracellular domain, hairy and enhancer of Split 1
and Delta-like protein 1 in renal tissue were all significantly decreased (
P
<0.05). The levels of GSH and SOD in renal tissue were significantly elevated (
P
<0.05). Moreover, the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group (
P
<0.05).
CONCLUSIONS
2
ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity, attenuation of renal oxidative stress, and suppression of aberrant Notch signaling pathway activation.
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