中华临床免疫和变态反应杂志
中華臨床免疫和變態反應雜誌
중화림상면역화변태반응잡지
Chinese Journal of Allergy & Clinical Immunology
2015年
3期
187-193
,共7页
许鸣华%李振彬%孙彩霞%陈萌%张征%杜勇
許鳴華%李振彬%孫綵霞%陳萌%張徵%杜勇
허명화%리진빈%손채하%진맹%장정%두용
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
雷公籐多苷%慢性移植物抗宿主病%狼瘡腎炎%高遷移率族蛋白-1%轉化生長因子-β1
뢰공등다감%만성이식물항숙주병%랑창신염%고천이솔족단백-1%전화생장인자-β1
tripterygium glycosides%chronic graft versus host disease%lupus nephritis%high mobility group box 1 protein%transforming growth factor β1
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， cGVHD）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）mg？24 h vs.（7.60±0.84）mg？24 h]、BUN [（6.74±1.00）mmol？L vs.（10.81±1.36）mmol？L]、SCr [（45.43±8.51）μmol？L vs.（130.48±8.82）μmol？L]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）mg？24 h vs.（4.65±0.50）mg？24 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[（0.4883±0.1032）vs.（0.1422±0.0414）]和 TGF-β1[（0.5038±0.0977）vs.（0.1477±0.0412）]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[（0.3165±0.0555）vs.（0.4040±0.0653）]和 TGF-β1[（0.3249±0.0593）vs.（0.4141±0.0701）]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 cGVHD 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。
目的：研究雷公籐多苷對狼瘡小鼠腎組織高遷移率族蛋白-1（high mobility group box 1 protein，HMGB-1）及轉化生長因子（transforming growth factor，TGF）-β1錶達的影響。方法建立慢性移植物抗宿主病（chronic graft versus host disease， cGVHD）狼瘡樣腎炎（lupus nephritis，LN）小鼠動物模型；取成模小鼠24隻，隨機分成 LN 模型組、醋痠潑尼鬆（Pred）組、來氟米特（LEF）組、雷公籐多苷（TG）組，每組6隻，在造模後第9週，分彆給予生理鹽水、Pred、LEF 及 TG，共28 d。于第12週末代謝籠留取24 h 尿液，檢測24 h 尿蛋白排洩率（urinary protein excretion，UPE）；第12週末痳醉心尖取血，檢測血清尿素氮（blood urea nitrogen，BUN）、血肌酐（serum creatine，SCr）含量；應用免疫組化方法檢測 HMGB-1及 TGF-β1在動物模型腎組織的錶達，同時分彆檢測瞭 Pred、LEF、TG 藥物榦預後，HMGB-1及 TGF-β1在病變組織中錶達的變化。結果與正常對照組相比，LN 組小鼠的 UPE [（1.40±0.50）mg？24 h vs.（7.60±0.84）mg？24 h]、BUN [（6.74±1.00）mmol？L vs.（10.81±1.36）mmol？L]、SCr [（45.43±8.51）μmol？L vs.（130.48±8.82）μmol？L]均顯著增高（P ＜0.01）。在降低 UPE 方麵，TG 組與 Pred 組差異具有統計學意義[（3.44±0.57）mg？24 h vs.（4.65±0.50）mg？24 h，P ＜0.05]。與 LN 組相比，榦預組小鼠腎髒病變均較 LN 組有所減輕，其中以 LEF 組、TG 組病變最輕，病理改變相似；LN 組小鼠腎髒組織中 HMGB-1[（0.4883±0.1032）vs.（0.1422±0.0414）]和 TGF-β1[（0.5038±0.0977）vs.（0.1477±0.0412）]錶達與正常對照組比較明顯增彊，差異有統計學意義（P ＜0.01）。榦預組較 LN 組小鼠腎髒組織中 HMGB-1和 TGF-β1錶達均明顯減弱，其中 TG組 HMGB-1[（0.3165±0.0555）vs.（0.4040±0.0653）]和 TGF-β1[（0.3249±0.0593）vs.（0.4141±0.0701）]減弱程度較 Pred 組更明顯，差異有統計學意義（P ＜0.05）。結論TG 及 Pred、LEF 能顯著下調 HMGB-l 和 TGF-β1在 cGVHD 狼瘡樣腎炎小鼠腎組織中的錶達，為臨床開展以 HMGB-l 等為靶點的 LN 治療提供瞭實驗依據。
목적：연구뢰공등다감대랑창소서신조직고천이솔족단백-1（high mobility group box 1 protein，HMGB-1）급전화생장인자（transforming growth factor，TGF）-β1표체적영향。방법건립만성이식물항숙주병（chronic graft versus host disease， cGVHD）랑창양신염（lupus nephritis，LN）소서동물모형；취성모소서24지，수궤분성 LN 모형조、작산발니송（Pred）조、래불미특（LEF）조、뢰공등다감（TG）조，매조6지，재조모후제9주，분별급여생리염수、Pred、LEF 급 TG，공28 d。우제12주말대사롱류취24 h 뇨액，검측24 h 뇨단백배설솔（urinary protein excretion，UPE）；제12주말마취심첨취혈，검측혈청뇨소담（blood urea nitrogen，BUN）、혈기항（serum creatine，SCr）함량；응용면역조화방법검측 HMGB-1급 TGF-β1재동물모형신조직적표체，동시분별검측료 Pred、LEF、TG 약물간예후，HMGB-1급 TGF-β1재병변조직중표체적변화。결과여정상대조조상비，LN 조소서적 UPE [（1.40±0.50）mg？24 h vs.（7.60±0.84）mg？24 h]、BUN [（6.74±1.00）mmol？L vs.（10.81±1.36）mmol？L]、SCr [（45.43±8.51）μmol？L vs.（130.48±8.82）μmol？L]균현저증고（P ＜0.01）。재강저 UPE 방면，TG 조여 Pred 조차이구유통계학의의[（3.44±0.57）mg？24 h vs.（4.65±0.50）mg？24 h，P ＜0.05]。여 LN 조상비，간예조소서신장병변균교 LN 조유소감경，기중이 LEF 조、TG 조병변최경，병리개변상사；LN 조소서신장조직중 HMGB-1[（0.4883±0.1032）vs.（0.1422±0.0414）]화 TGF-β1[（0.5038±0.0977）vs.（0.1477±0.0412）]표체여정상대조조비교명현증강，차이유통계학의의（P ＜0.01）。간예조교 LN 조소서신장조직중 HMGB-1화 TGF-β1표체균명현감약，기중 TG조 HMGB-1[（0.3165±0.0555）vs.（0.4040±0.0653）]화 TGF-β1[（0.3249±0.0593）vs.（0.4141±0.0701）]감약정도교 Pred 조경명현，차이유통계학의의（P ＜0.05）。결론TG 급 Pred、LEF 능현저하조 HMGB-l 화 TGF-β1재 cGVHD 랑창양신염소서신조직중적표체，위림상개전이 HMGB-l 등위파점적 LN 치료제공료실험의거。
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?L vs.(10.81 ±1.36)mmol?L]and SCr level [(45.43 ±8.51)μmol?L vs.(130.48 ±8.82)μmol?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 <0.01)while the expression of HMGB-1 and TGF-β1 in the intervention group was less compared with the LN group (P <0.01 or P <0.05).The expression in TII group was less compared with Pred group [HMGB-1:(0.316 5 ±0.055 5)vs.(0.404 0 ±0.065 3);TGF-β1:(0.324 9 ±0.059 3)vs.(0.414 1 ±0.070 1)](P <0.05).Conclusions The study on the inhibitory effect of Pred,LEF and TII on the expression of HMGB1 and TGF-β1 in kidney tissues of cGVHD LN mice models has provided experimental basis for anti-HMGB1 therapy integrating Chinese traditional medicine and western medicine.
