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牛磺酸通过使核因子κB通路失活减轻狼疮性肾炎小鼠的损伤。

Taurine attenuates the damage of lupus nephritis mouse via inactivation of the NF-κB pathway.

作者信息

Luo Huan, Geng Chun-Jie, Miao Shi-Min, Wang Li-Hua, Li Qiang

机构信息

Division of Rheumatology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.

Department of Dermatology and Sexually Transmitted Diseases, The Third Hospital of Xingtai, Xingtai, China.

出版信息

Ann Palliat Med. 2021 Jan;10(1):137-147. doi: 10.21037/apm-20-2087.

DOI:10.21037/apm-20-2087
PMID:33545753
Abstract

BACKGROUND

Taurine is an organic amino acid and a major constituent of bile. With its contribution to various cellular functions, it has demonstrated therapeutic effects in a wide range of diseases. Since there is a lack of literature investigating taurine as a treatment for lupus nephritis (LN), here we examined the potential of taurine as a treatment for LN.

METHODS

Experiments were carried out using MRL/lpr mice as a model of LN, and C57BL/6 mice were used as negative controls. At 12 weeks old, MRL/lpr mice were divided into four groups and treated with 0, 50 and 100 mg/kg body weight taurine for 5 days. Enalapril is used as a positive control drug. All animals were sacrificed after treatment. LN-induced damage was assessed by proteinuria, blood urea nitrogen (BUN) and serum creatinine (CRE) levels. The degree of inflammation was assessed by inducible nitric oxide synthase (iNOS), interleukin-4 (IL-4), IL-10, and tumor necrosis factor-α (TNF-α) levels. The degree of oxidative stress was assessed by malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (Gpx) levels. Hematoxylin and eosin (HE) staining and TUNEL staining assessed histopathological damage and apoptosis, respectively. The levels of Bcl-2, Bax, caspase-3, caspase-9, and NF-κB p65 were detected by western blot.

RESULTS

The data indicated that taurine administration improved kidney functions, reversed cell death, suppressed oxidative stress, and importantly, adjusted the immune response of LN mice to a more balanced state.

CONCLUSIONS

These results provide a novel strategy for LN therapy, which may overcome the disadvantages of traditional immunosuppression and hormone treatments with greater efficacy and fewer side effects.

摘要

背景

牛磺酸是一种有机氨基酸,是胆汁的主要成分。它对多种细胞功能有作用,已在多种疾病中显示出治疗效果。由于缺乏关于牛磺酸治疗狼疮性肾炎(LN)的文献,我们在此研究了牛磺酸治疗LN的潜力。

方法

实验以MRL/lpr小鼠作为LN模型,C57BL/6小鼠作为阴性对照。12周龄时,将MRL/lpr小鼠分为四组,分别用0、50和100mg/kg体重的牛磺酸处理5天。依那普利用作阳性对照药物。治疗后处死所有动物。通过蛋白尿、血尿素氮(BUN)和血清肌酐(CRE)水平评估LN诱导的损伤。通过诱导型一氧化氮合酶(iNOS)、白细胞介素-4(IL-4)、IL-10和肿瘤坏死因子-α(TNF-α)水平评估炎症程度。通过丙二醛(MDA)、活性氧(ROS)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(Gpx)水平评估氧化应激程度。苏木精和伊红(HE)染色和TUNEL染色分别评估组织病理学损伤和细胞凋亡。通过蛋白质印迹法检测Bcl-2、Bax、半胱天冬酶-3、半胱天冬酶-9和核因子-κB p65的水平。

结果

数据表明,给予牛磺酸可改善肾功能,逆转细胞死亡,抑制氧化应激,重要的是,将LN小鼠的免疫反应调节至更平衡的状态。

结论

这些结果为LN治疗提供了一种新策略,可能克服传统免疫抑制和激素治疗的缺点,具有更高的疗效和更少的副作用。

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