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青蒿素联合糖皮质激素对狼疮肾炎小鼠糖皮质激素受体 αmRNA、糖皮质激素受体 βmRNA 和 P300/CBP 蛋白表达的影响。

Effect of artemisinin combined with glucocorticoid on the expressions of glucocorticoid receptor α mRNA, glucocorticoid receptor β mRNA and P300/CBP protein in lupus nephritis mice.

机构信息

Department of Integrated Chinese Traditional and Western Medicine, Shaanxi Province Key Traditional Chinese Medicine, Department of Nephrology, Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an (710004), China.

出版信息

Chin J Integr Med. 2011 Apr;17(4):277-82. doi: 10.1007/s11655-011-0693-3. Epub 2011 Apr 21.

Abstract

OBJECTIVE

To investigate the therapeutic effects and mechanisms of using artemisinin (Art) combined with glucocorticoid (GC) to treat lupus nephritis (LN) mice.

METHODS

Forty hybrid female mice were randomly and equally divided into four groups with the method of random number table: control group, model group, prednisone group administrated with 6.45 mg/(kg·d) prednisone suspension, and Art+prednisone group administrated with 150 mg/(kg·d) Art suspension and 3.225 mg/(kg·d) prednisone suspension. A mice model of LN was established by injection with living lymph cell suspension. The changes of urine protein/24h, the expressions of GC receptor α (GRα) mRNA, GC receptor β (GRβ) mRNA in peripheral blood mononuclear cells (PBMCs), and transcriptional coactivator P300/CBP protein in renal tissue were measured.

RESULTS

Compared with the model group, the treatment groups had significant decrease in urine protein/24 h, and renal pathological lesion (P<0.01). In the same groups, the expression of transcriptional coactivator P300/CBP protein in renal tissue and GRα mRNA were significantly increased, and GRβ mRNA expression was significantly decreased (P<0.01). And the Art+prednisone group has a better therapeutic effect than the prednisone group (P<0.01).

CONCLUSIONS

Art has therapeutic sensitization effects on GC in the LN mice. The underlying mechanism could be correlated with the effect of Art on the increase of the expressions of GRα mRNA and transcriptional coactivator P300 300/CBP protein in renal tissue and on the decrease of the expression of GRβ mRNA in PBMC.

摘要

目的

研究青蒿素(Art)联合糖皮质激素(GC)治疗狼疮肾炎(LN)小鼠的疗效及作用机制。

方法

40 只雌性杂交小鼠采用随机数字表法随机分为 4 组,每组 10 只:对照组、模型组、泼尼松组给予 6.45 mg/(kg·d)泼尼松混悬液、青蒿素+泼尼松组给予 150 mg/(kg·d)青蒿素混悬液和 3.225 mg/(kg·d)泼尼松混悬液。通过注射活淋巴细胞悬液建立 LN 小鼠模型。检测各组小鼠 24 h 尿蛋白、外周血单个核细胞(PBMCs)中 GC 受体α(GRα)mRNA、GC 受体β(GRβ)mRNA 的表达及肾组织转录共激活因子 P300/CBP 蛋白的变化。

结果

与模型组比较,各治疗组小鼠 24 h 尿蛋白减少,肾脏病理损伤减轻(P<0.01);同一组中,肾组织转录共激活因子 P300/CBP 蛋白和 GRα mRNA 表达明显增加,GRβ mRNA 表达明显降低(P<0.01);青蒿素+泼尼松组的疗效优于泼尼松组(P<0.01)。

结论

青蒿素对 LN 小鼠 GC 具有治疗增敏作用,其作用机制可能与青蒿素增加肾组织中 GRα mRNA 和转录共激活因子 P300/CBP 蛋白的表达以及降低 PBMC 中 GRβ mRNA 的表达有关。

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