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雷公藤多苷改善肾病综合征大鼠模型异常脂质沉积。

Tripterygium glycosides improve abnormal lipid deposition in nephrotic syndrome rat models.

机构信息

Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.

Guangzhou Key Laboratory of Chirality Research on Active Components of Traditional Chinese Medicine, Guangzhou, China.

出版信息

Ren Fail. 2023 Dec;45(1):2182617. doi: 10.1080/0886022X.2023.2182617.

Abstract

OBJECTIVE

The purpose of this study was to determine the effect of tripterygium glycosides (TGs) on regulating abnormal lipid deposition in nephrotic syndrome (NS) rats.

METHODS

Sprague-Dawley (SD) rats were injected with 6 mg/kg doxorubicin to construct nephrotic syndrome models ( = 6 per group), and then administered with TGs (10 mg/kg·d), prednisone (6.3 mg/kg·d), or pure water for 5 weeks. Biomedical indexes, such as urine protein/creatinine ratio (PCR), blood urea nitrogen (BUN), serum creatinine (Scr), serum albumin (SA), triglycerides (TG), total cholesterol (TC)were investigated to evaluate the renal injury of rats. H&E staining experiment was used to assess the pathological alterations. Oil Red O staining was used to assess the level of renal lipid deposition. Malondialdehyde (MDA) and glutathione (GSH) were measured to assess the extent of oxidative damage to the kidney. TUNEL staining was used to assess the status of apoptosis in the kidney. Western blot analysis was performed to examine the levels of relevant intracellular signaling molecules.

RESULTS

After treatment with TGs, those tested biomedical indexes were significantly improved, and the extent of kidney tissue pathological changes and lipid deposition in the kidney was diminished. Treatment with TGs decreased renal oxidative damage and apoptosis. Regarding the molecular mechanism, TGs significantly increased the protein expression levels of Bcl-2 but decreased the levels of CD36, ADFP, Bax, and Cleaved caspase-3.

CONCLUSION

TGs alleviates renal injury and lipid deposition induced by doxorubicin, suggesting that it may be a new strategy for reducing renal lipotoxicity in NS.

摘要

目的

本研究旨在探讨雷公藤多苷(TGs)对肾病综合征(NS)大鼠异常脂质沉积的调节作用。

方法

采用 6mg/kg 阿霉素腹腔注射构建肾病综合征大鼠模型(每组 6 只),然后分别给予 TGs(10mg/kg·d)、泼尼松(6.3mg/kg·d)或生理盐水治疗 5 周。检测大鼠的尿蛋白/肌酐比(PCR)、血尿素氮(BUN)、血清肌酐(Scr)、血清白蛋白(SA)、甘油三酯(TG)、总胆固醇(TC)等生物医学指标,评估大鼠的肾脏损伤情况。H&E 染色实验评估大鼠的病理改变。油红 O 染色评估肾脏脂质沉积水平。测定丙二醛(MDA)和谷胱甘肽(GSH)评估肾脏氧化损伤程度。TUNEL 染色评估肾脏细胞凋亡状态。Western blot 分析检测相关细胞内信号分子的水平。

结果

经 TGs 治疗后,大鼠的生物医学指标明显改善,肾脏组织病理变化和肾脏脂质沉积程度减轻。TGs 治疗可降低肾脏氧化损伤和细胞凋亡。从分子机制上看,TGs 可显著增加 Bcl-2 蛋白表达水平,降低 CD36、ADFP、Bax 和 Cleaved caspase-3 水平。

结论

TGs 减轻阿霉素诱导的肾脏损伤和脂质沉积,提示其可能是减少 NS 肾脂毒性的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9170/10013393/d7ac96fb3b52/IRNF_A_2182617_UF0001_C.jpg

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