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血必净注射液对系统性红斑狼疮小鼠的影响。

Effect of Xuebijing injection on systemic lupus erythematosus in mice.

机构信息

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

出版信息

Chin J Integr Med. 2013 Sep;19(9):675-82. doi: 10.1007/s11655-013-1561-0. Epub 2013 Aug 24.

Abstract

OBJECTIVE

To observe the effects of Xuebijing injection on dendritic cells (DCs) and T lymphocytes, and the potential mechanisms of its therapeutic effect on systemic lupus erythematosus (SLE).

METHODS

A widely used mouse model, SLE-prone BLLF1 mice aged 8-10 weeks, was employed. Mice were randomly divided into 4 groups: a normal group, a model group and two treatment groups treated with Xuebijing Injection with a dose of 6.4 mL/kg via intraperitoneal administration for SLE-prone BLLF1 mice aged 8 weeks (treatment A group) and 10 weeks (treatment B group). Renal tissue sections were stained with Masson's trichrome and periodic acid-silver methenamine. Histopathological changes in the kidney were evaluated by a light microscopy. The capacity of the DCs isolated from the spleen to stimulate the T cell proliferation in response to concanavalin A (Con A) was determined.

RESULTS

Compared with the model group, levels of anti-dsDNA antibodies in the two treatment groups decreased remarkablly (P<0.01, P<0.05), and levels of serum creatinine and blood urea nitrogen increased (P<0.01, P<0.05). Pathological changes were found in the kidney in the model group. Histopathological abnormalities were alleviated in the two treatment groups. Treatment with Xuebijing injection also significantly upregulated the expression of CD80, CD86 and major histocompatibility class II by DCs compared with the model group (P<0.05). When splenic T lymphocytes from BLLF1 mice were co-cultured with DCs at ratios of 1:100, 1:150 and 1:200 for 3 and 5 days, the proliferation of T lymphocytes was suppressed compared with the normal group (P<0.05), but this was restored by Xuebijing Injection under the same conditions. In the model group, levels of tumor necrosis factor (TNF)-α in supernatants were significantly elevated compared with the normal group (P<0.01), interleukin-2 levels decreased (P<0.05), while these changes were significantly alleviated in the Xuebijing treatment groups.

CONCLUSIONS

Xuebijing Injection alleviated renal injury in SLE-prone BLLF-1 mice. The mechanism might be through influencing T cell polarization mediated by DCs, and Xuebijing Injection might be a potential drug that suppresses immune dysfunction in patients with SLE.

摘要

目的

观察血必净注射液对树突状细胞(DC)和 T 淋巴细胞的影响,探讨其治疗系统性红斑狼疮(SLE)的作用机制。

方法

采用 8~10 周龄的狼疮易感 BLLF1 小鼠作为研究对象,随机分为正常组、模型组和血必净治疗组,每组又分为两个亚组,即分别于 8 周龄和 10 周龄时腹腔注射血必净注射液 6.4mL/kg 的治疗 A 组和治疗 B 组。Masson 三色染色和过碘酸雪夫染色观察肾脏组织病理学改变,光镜下观察肾脏病理变化。分离脾脏树突状细胞(DC),用刀豆蛋白 A(ConA)刺激其增殖,检测 DC 刺激 T 淋巴细胞增殖的能力。

结果

与模型组相比,两治疗组抗双链 DNA 抗体水平显著降低(P<0.01,P<0.05),血肌酐和血尿素氮水平显著升高(P<0.01,P<0.05);模型组小鼠肾脏组织出现病理改变,两治疗组病理变化明显减轻。与模型组相比,两治疗组 DC 表面分子 CD80、CD86 和主要组织相容性复合体Ⅱ的表达显著上调(P<0.05)。当以 1:100、1:150 和 1:200 的比例将 BLLF1 小鼠的脾 T 细胞与 DC 共培养 3 天和 5 天时,与正常组相比,T 淋巴细胞增殖受到抑制(P<0.05),但在相同条件下,血必净可恢复 T 淋巴细胞的增殖。与正常组相比,模型组上清液中肿瘤坏死因子-α水平显著升高(P<0.01),白细胞介素-2 水平降低(P<0.05),而血必净治疗组这些变化明显减轻。

结论

血必净注射液可减轻狼疮易感 BLLF1 小鼠的肾脏损伤,其作用机制可能与影响 DC 介导的 T 细胞极化有关,血必净可能是一种抑制 SLE 患者免疫功能紊乱的潜在药物。

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