摘要
目的研究雷公藤多苷对狼疮小鼠肾组织高迁移率族蛋白-1(high mobility group box 1 protein,HMGB-1)及转化生长因子(transforming growth factor,TGF)-β1表达的影响。方法建立慢性移植物抗宿主病(chronic graft versus host disease,c GVHD)狼疮样肾炎(lupus nephritis,LN)小鼠动物模型;取成模小鼠24只,随机分成LN模型组、醋酸泼尼松(Pred)组、来氟米特(LEF)组、雷公藤多苷(TG)组,每组6只,在造模后第9周,分别给予生理盐水、Pred、LEF及TG,共28 d。于第12周末代谢笼留取24 h尿液,检测24 h尿蛋白排泄率(urinary protein excretion,UPE);第12周末麻醉心尖取血,检测血清尿素氮(blood urea nitrogen,BUN)、血肌酐(serum creatine,SCr)含量;应用免疫组化方法检测HMGB-1及TGF-β1在动物模型肾组织的表达,同时分别检测了Pred、LEF、TG药物干预后,HMGB-1及TGF-β1在病变组织中表达的变化。结果与正常对照组相比,LN组小鼠的UPE[(1.40±0.50)mg24 h vs.(7.60±0.84)mg24 h]、BUN[(6.74±1.00)mmolL vs.(10.81±1.36)mmolL]、SCr[(45.43±8.51)μmolL vs.(130.48±8.82)μmolL]均显著增高(P<0.01)。在降低UPE方面,TG组与Pred组差异具有统计学意义[(3.44±0.57)mg24 h vs.(4.65±0.50)mg24 h,P<0.05]。与LN组相比,干预组小鼠肾脏病变均较LN组有所减轻,其中以LEF组、TG组病变最轻,病理改变相似;LN组小鼠肾脏组织中HMGB-1[(0.488 3±0.103 2)vs.(0.142 2±0.041 4)]和TGF-β1[(0.503 8±0.097 7)vs.(0.147 7±0.041 2)]表达与正常对照组比较明显增强,差异有统计学意义(P<0.01)。干预组较LN组小鼠肾脏组织中HMGB-1和TGF-β1表达均明显减弱,其中TG组HMGB-1[(0.316 5±0.055 5)vs.(0.404 0±0.065 3)]和TGF-β1[(0.324 9±0.059 3)vs.(0.414 1±0.070 1)]减弱程度较Pred组更明显,差异有统计学意义(P<0.05)。结论 TG及Pred、LEF能显著下调HMGB-l和TGF-β1在c GVHD狼疮样肾炎小鼠肾组织中的表达,为临床开展以HMGB-l等为靶点的LN治疗提供了实验依据。
Objective To observe the effect of tripterygium Hook II （TII） high mobility group box 1 protein （HMGB1） on the expression of kidney tissues of cGVHD lupus nephritis （LN） mice models. Methods The cGVHD LN mice models were established and twenty-four mice models were randomly divided into the LN group, the prednisone （Pred） group, the lefunomide （LEF） group and the TII group, 6 mice in each group. In the 9th week after establishment, the mice models were given normal saline, Pred, LEF and TG respectively for 28 days. Their 24 hour urine protein excretion （UPE） level were measured respectively at the end of 12th week and the serum BUN and SCr levels were also measured at the end of 12th week. Immuneohistochemistry was used to test the expression of HMGB-1 and TGF- β1 in kidney tissues of the model mice, meanwhile the expressions of HMGB-1 and TGF- β1 in kideny tissues after Pred, LEF and TII were also tested. Results UPE [ （ 1.40 ± 0. 50） mg/24 h vs. （7.60± 0. 84） mg/24 h ], serum BUN [ （6. 74± 1.00） mmol/Lvs. （10.81 ±1.36） mmol/L] and SCr level [（45.43±8.51） μmol/L vs. （130.48 ±8.82） mol/L] of the LN group was obviously higher when compared with that of the control group, while they were obviously lower in the intervention group when compared with the LN group （P 〈 0. 05 ）. There was significant difference between the TII group and the Pred group in UPE reduction [ （3.44 ±0. 57） mg/24 h vs. （4. 65 ± 0. 50） mg/24 h, P 〈 0. 05 ] , while there was no obvious difference between the TII group and the LEF group in lowering serum UPE, BUN and SCr levels. Renal pathological changes in the intervention group were less than those in the LN group and the pathological changes in the LEF and the TII group were the least but similar. The expression of HMGB-1 [（0.488 3 ±0.103 2） vs. （0.142 2 ±0.041 4）] and TGF-β1 [（0.503 8±0.097 7） vs. （0. 147 7 ±0.041 2）] in the LN group was obviously higher than that of the control group （P 〈 0.
出处
《中华临床免疫和变态反应杂志》
2015年第3期187-193,I0004,I0005,共9页
Chinese Journal of Allergy & Clinical Immunology
关键词
雷公藤多苷
慢性移植物抗宿主病
狼疮肾炎
高迁移率族蛋白-1
转化生长因子-β1
tripterygium glycosides
chronic graft versus host disease
lupus nephritis
high mobility group box 1 protein
transforminggrowth factor β1
