| 郎茜,龚蕾,车蓉,等.杜仲多糖对糖尿病大鼠肾脏损伤的作用机制[J].安徽医药,2026,30(1):60-66. |
| 杜仲多糖对糖尿病大鼠肾脏损伤的作用机制 |
| Effects and action mechanism of Eucommia ulmoides polysaccharide for renal damage in diabetic rats |
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| DOI：10.3969/j.issn.1009-6469.2026.01.013 |
| 中文关键词: 杜仲 糖尿病 肾脏损伤 氧化应激 凋亡 |
| 英文关键词: Eucommia bark Diabetes mellitus Renal damage Oxidative stress Apoptosis |
| 基金项目:云南省教育厅科学研究基金项目( 2021J1114) |
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| 中文摘要: |
| 目的明确杜仲多糖对糖尿病大鼠肾脏功能损伤的保护作用并初步探究其作用机制。方法 2021年 12月至 2023年 6月，将雄性 SD大鼠 72只，抽取 12只作为正常组，其余按照 30 mg/kg的剂量腹腔注射链脲佐菌素( STZ)，建立糖尿病肾脏损伤模型。将成功建模的 SD大鼠，分成模型组和杜仲多糖低剂量实验组( 50 mg/kg)、中剂量实验组( 100 mg/kg)、高剂量实验组( 200 mg/kg)及二甲双胍组( 200 mg/kg)，每组 12只。连续给药干预 7d后，每组选取 6只大鼠进行研究，剩下大鼠继续给药干预 7d，取材并对各组大鼠空腹血糖( FBG)、体质量、肾脏指数、血清尿素氮( BUN)、肾组织匀浆液中丙二醛含量、总超氧化物歧化酶( T-SOD)以及谷胱甘肽过氧化物酶( GSH-Px)活力、肾组织受损的病理情况、肾组织转化生长因子 -β1(TGF-β1)、 p38丝裂原活化蛋白激酶( p38MAPK)、胱天蛋白酶 -3(caspase-3)等因子进行分析。结果与模型组相比，杜仲多糖低、中、高剂量实验组大鼠体质量显著增加( P<0.05)，高剂量实验组及二甲双胍组的大鼠肾脏指数显著降低( P<0.05)。同时，给药 14 d后，与模型组大鼠 FBG、BUN［( 19.40±1.81)mmol/L、(14.66±1.48)mmol/L］比较，高剂量实验组大鼠 FBG、BUN［( 10.60±1.28) mmol/L、(6.19±0.91)mmol/L］均显著降低( P<0.05)。病理学结果显示，杜仲多糖的干预可以缓解糖尿病大鼠肾脏病变程度且呈剂量依赖，剂量越高对大鼠肾小管上皮细胞肿胀空泡化的缓解作用越强。在氧化应激指标方面，与模型组比较，高剂量实验组能显著降低丙二醛含量，并提升 T-SOD与 GSH-Px活力(P<0.05)。在该研究中，对糖尿病大鼠给药干预 7d和 14 d后，提取了大鼠肾脏组织的总蛋白，测定了组织中 TGF-β1、p38 MAPK及 caspase-3蛋白的表达情况，结果显示，给药干预 14 d后，模型组 TGF-β1、p38 MAPK以及 caspase-3表达量仍显著高于正常组( P<0.05)，高剂量实验组 TGF-β1、p38 MAPK、caspase-3显著低于模型组( P<0.05)。结论杜仲多糖可以显著降低糖尿病大鼠的血糖，其改善糖尿病大鼠体质量、肾脏指数、血清 BUN含量、抗氧化能力与二甲双胍效果相当，且呈剂量、时间依赖。同时，杜仲多糖可减轻肾小球内淤血和肾小管上皮细胞空泡化。随着杜仲多糖剂量的增加， TGF-β1、p38MAPK、细胞凋亡重要效应因子 caspase-3的表达水平下调越明显。 |
| 英文摘要: |
| Objective To clarify the protective effect and potetial mechanism of Eucommia ulmoides polysaccharide on renal damage of diabetic rats.Methods From December 2021 to June 2023, 12 male SD rats were randomly selected from 72 rats as the normalgroup, while the rest were intraperitoneally injected with streptozotocin (STZ) at a dose of 30 mg/kg to establish a diabetic kidney injurymodel. The diabetic SD rats were randomly divided into model group, low-dose (50 mg/kg), medium-dose (100 mg/kg) and high-dose (200 mg/kg) Eucommia ulmoides polysaccharide experimental groups, and metformin group, with 12 rats in each group. After 7 days ofcontinuous administration, 6 rats were randomly selected from each group for analysis, while the remaining rats continued to receive ad-ministration for another 7 days. Fasting blood glucose (FBG), body weight, renal index, serum blood urea nitrogen (BUN), content ofmalondialdehyde (MDA) in kidney homogenate, total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activity were measured, meanwhile, the expression levels of transforming growth factor-β1 (TGF-β1), p38 mitogen activated protein kinase (p38-MAPK) and cysteine aspartate specific protease-3 (caspase-3) in rat kidney of each group were detected.Results Compared with the model group, the weight of rats in low-, medium- and high-dose groups of Eucommia ulmoides polysaccharide increased significantly (P< 0.05), while the renal index in the high-dose experimental group and metformin group decreased significantly (P<0.05). Meanwhile, af-ter 14 days of administration, compared with the model group, FBG [(10.60±1.28) mmol/L vs. (19.40±1.81) mmol/L] and BUN [(6.19±0.91) mmol/L vs. (14.66±1.48) mmol/L] in the high-dose experimental group were significantly decreased (P<0.05). Pathological results showed that the intervention of Eucommia ulmoides polysaccharide could alleviate the degree of renal lesions in diabetic rats in a dose-dependent manner; the higher the dose administered, the stronger the relieving efficacy in the swelling and vacuolization of rat renal tu-bular epithelial cells. Regarding oxidative stress indicators, compared with the model group, the high-dose experimental group signifi-cantly reduced MDA and increased the activities of T-SOD and GSH-Px (P<0.05). In this study, total protein was extracted from the kid-ney tissue of diabetic rats after 7 and 14 days of drug intervention, and the levels of TGF-β1, p38 MAPK, and caspase-3 in renal tissue were measured. The results showed that after 14 days of intervention, the expression levels of TGF-β1, p38 MAPK, and caspase-3 in the model group were still significantly higher than those in the normal group (P<0.05), and the expression levels of TGF-β1 , p38 MAPK and caspase-3 in the high-dose group were significantly lower than those in the model group(P<0.05).Conclusions Eucommia ulmoides polysaccharide can significantly reduce FBG, whose effect on improving body weight, kidney index, serum BUN content, andantioxidant capacity of diabetic rats is comparable to that of metformin in a dose-and time-dependent manne r. Furthermore, Eucommia ulmoides polysaccharide can reduce the internal glomerular stasis and vacuolation of renal tubular epithelial cells. Increasing doses ofEucommia ulmoides polysaccharide leads to a progressive downregulation in the expression of TGF-β1, p38MAPK, and the key apoptot-ic effector caspase-3. |
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