中华危重病急救医学
中華危重病急救醫學
중화위중병급구의학
Chinese Critical Care Medicine
2014年
3期
188-192
,共5页
陈明祺%鲁俊%程璐%吕海%王醒
陳明祺%魯俊%程璐%呂海%王醒
진명기%로준%정로%려해%왕성
脓毒症%四逆汤%炎症反应失衡%免疫功能%肠道功能%大鼠
膿毒癥%四逆湯%炎癥反應失衡%免疫功能%腸道功能%大鼠
농독증%사역탕%염증반응실형%면역공능%장도공능%대서
Sepsis%Sini decoction%Inflammatory response disequilibrium%Immune function%Intestinal function%Rat
目的 观察四逆汤对脓毒症大鼠炎症反应及免疫功能的影响,并探讨其可能的作用机制.方法 66只SD大鼠按随机数字表法分为正常对照组(n=6)、模型组(n=30)和四逆汤组(n=30).腹腔注射脂多糖(LPS)5 mg/kg制备脓毒症大鼠模型.四逆汤组于制模后即刻灌胃四逆汤5 g/kg;模型组给予等量生理盐水；正常对照组不予任何处理.分别于制模后2、12、24、48、72 h经眼眶采血后处死大鼠,采用酶联免疫吸附试验(ELISA)测定血清白细胞介素(IL-1、IL-6、IL-10)、肿瘤坏死因子-α(TNF-α)及单核细胞人白细胞DR抗原(HLA-DR)表达水平,并观察肠黏膜组织病理改变.结果 制模后2h模型组IL-1水平(ng/L)即逐渐升高,至48 h达峰值(4.07±0.10)后逐渐下降；四逆汤组则于制模后12h达峰值(2.98±0.12)后逐渐下降.模型组和四逆汤组IL-6水平(ng/L)分别于制模后12 h(91.39± 1.55、73.00±2.38)、48 h(82.51±1.49、64.68±1.68)达到两个高峰.模型组IL-10水平(ng/L)于制模后2h达高峰(86.66±6.12)后逐渐下降；四逆汤组于制模后12h短暂下降(71.61±2.35)后逐渐上升,至48 h接近正常对照组水平(109.09±4.77比124.01±7.89,P＞0.05).模型组TNF-α水平(ng/L)逐渐升高至48 h达峰值(83.37±3.79)；四逆汤组升高至12h达峰值(48.52±1.21),72 h降到正常对照组水平(18.59±1.97比15.50±2.68,P＞0.05).实验过程中,与模型组比较,四逆汤组各时间点IL-1、IL-6、TNF-α明显下降,IL-10明显升高.模型组和四逆汤组HLA-DR表达(μg/L)于制模后2h达峰值(4.86±0.15、4.85±0.17),随后逐渐下降；四逆汤组于制模后48 h和72 h时HLA-DR表达较模型组显著升高(48 h:4.21±0.12比2.74±0.16,72h:3.80±0.09比2.27±0.12,均P＜0.01).光镜下观察显示:制模后2h,模型组和四逆汤组肠黏膜均有明显炎性细胞浸润,绒毛受损严重；于制模后12h起,四逆汤组炎性细胞浸润较模型组明显减轻,小肠黏膜绒毛修复较模型组更完整.结论 四逆汤可调节脓毒症大鼠全身炎症反应状态,促进肠黏膜的修复,保护肠道功能,并促进机体免疫功能的恢复.
目的 觀察四逆湯對膿毒癥大鼠炎癥反應及免疫功能的影響,併探討其可能的作用機製.方法 66隻SD大鼠按隨機數字錶法分為正常對照組(n=6)、模型組(n=30)和四逆湯組(n=30).腹腔註射脂多糖(LPS)5 mg/kg製備膿毒癥大鼠模型.四逆湯組于製模後即刻灌胃四逆湯5 g/kg;模型組給予等量生理鹽水；正常對照組不予任何處理.分彆于製模後2、12、24、48、72 h經眼眶採血後處死大鼠,採用酶聯免疫吸附試驗(ELISA)測定血清白細胞介素(IL-1、IL-6、IL-10)、腫瘤壞死因子-α(TNF-α)及單覈細胞人白細胞DR抗原(HLA-DR)錶達水平,併觀察腸黏膜組織病理改變.結果 製模後2h模型組IL-1水平(ng/L)即逐漸升高,至48 h達峰值(4.07±0.10)後逐漸下降；四逆湯組則于製模後12h達峰值(2.98±0.12)後逐漸下降.模型組和四逆湯組IL-6水平(ng/L)分彆于製模後12 h(91.39± 1.55、73.00±2.38)、48 h(82.51±1.49、64.68±1.68)達到兩箇高峰.模型組IL-10水平(ng/L)于製模後2h達高峰(86.66±6.12)後逐漸下降；四逆湯組于製模後12h短暫下降(71.61±2.35)後逐漸上升,至48 h接近正常對照組水平(109.09±4.77比124.01±7.89,P＞0.05).模型組TNF-α水平(ng/L)逐漸升高至48 h達峰值(83.37±3.79)；四逆湯組升高至12h達峰值(48.52±1.21),72 h降到正常對照組水平(18.59±1.97比15.50±2.68,P＞0.05).實驗過程中,與模型組比較,四逆湯組各時間點IL-1、IL-6、TNF-α明顯下降,IL-10明顯升高.模型組和四逆湯組HLA-DR錶達(μg/L)于製模後2h達峰值(4.86±0.15、4.85±0.17),隨後逐漸下降；四逆湯組于製模後48 h和72 h時HLA-DR錶達較模型組顯著升高(48 h:4.21±0.12比2.74±0.16,72h:3.80±0.09比2.27±0.12,均P＜0.01).光鏡下觀察顯示:製模後2h,模型組和四逆湯組腸黏膜均有明顯炎性細胞浸潤,絨毛受損嚴重；于製模後12h起,四逆湯組炎性細胞浸潤較模型組明顯減輕,小腸黏膜絨毛脩複較模型組更完整.結論 四逆湯可調節膿毒癥大鼠全身炎癥反應狀態,促進腸黏膜的脩複,保護腸道功能,併促進機體免疫功能的恢複.
목적 관찰사역탕대농독증대서염증반응급면역공능적영향,병탐토기가능적작용궤제.방법 66지SD대서안수궤수자표법분위정상대조조(n=6)、모형조(n=30)화사역탕조(n=30).복강주사지다당(LPS)5 mg/kg제비농독증대서모형.사역탕조우제모후즉각관위사역탕5 g/kg;모형조급여등량생리염수；정상대조조불여임하처리.분별우제모후2、12、24、48、72 h경안광채혈후처사대서,채용매련면역흡부시험(ELISA)측정혈청백세포개소(IL-1、IL-6、IL-10)、종류배사인자-α(TNF-α)급단핵세포인백세포DR항원(HLA-DR)표체수평,병관찰장점막조직병리개변.결과 제모후2h모형조IL-1수평(ng/L)즉축점승고,지48 h체봉치(4.07±0.10)후축점하강；사역탕조칙우제모후12h체봉치(2.98±0.12)후축점하강.모형조화사역탕조IL-6수평(ng/L)분별우제모후12 h(91.39± 1.55、73.00±2.38)、48 h(82.51±1.49、64.68±1.68)체도량개고봉.모형조IL-10수평(ng/L)우제모후2h체고봉(86.66±6.12)후축점하강；사역탕조우제모후12h단잠하강(71.61±2.35)후축점상승,지48 h접근정상대조조수평(109.09±4.77비124.01±7.89,P＞0.05).모형조TNF-α수평(ng/L)축점승고지48 h체봉치(83.37±3.79)；사역탕조승고지12h체봉치(48.52±1.21),72 h강도정상대조조수평(18.59±1.97비15.50±2.68,P＞0.05).실험과정중,여모형조비교,사역탕조각시간점IL-1、IL-6、TNF-α명현하강,IL-10명현승고.모형조화사역탕조HLA-DR표체(μg/L)우제모후2h체봉치(4.86±0.15、4.85±0.17),수후축점하강；사역탕조우제모후48 h화72 h시HLA-DR표체교모형조현저승고(48 h:4.21±0.12비2.74±0.16,72h:3.80±0.09비2.27±0.12,균P＜0.01).광경하관찰현시:제모후2h,모형조화사역탕조장점막균유명현염성세포침윤,융모수손엄중；우제모후12h기,사역탕조염성세포침윤교모형조명현감경,소장점막융모수복교모형조경완정.결론 사역탕가조절농독증대서전신염증반응상태,촉진장점막적수복,보호장도공능,병촉진궤체면역공능적회복.
Objective To observe the effect of Sini decoction on inflammatory response and immune function in septic rats and to discuss its possible mechanism.Methods 66 Sprague-Dawley (SD) rats were randomly divided into normal control group (n=6),model group (n=30),and Sini decoction group (n=30).Septic model was reproduced by intraperitoneal injection of lipopolysaccharide (LPS,5 mg/kg).After the reproduction of sepsis,rats in Sini decoction group received Sini decoction (5 g/kg) by gavage,while those in model group were given equal dose of normal saline in the same way.Rats in normal control group did not receive any treatment.Blood was collected via eye sockets at 2,12,24,48,72 hours after LPS administration,then the rats were sacrificed.The concentrations of inflammatory mediators,such as interleukin (IL-1,IL-6,IL-10),tumor necrosis factor-α (TNF-α),and the expression level of monocyte human leukocyte antigen-DR (HLA-DR) were determined with enzyme linked immunosorbent assay (ELISA),and the pathological changes in intestinal mucosa were observed under electron microscope.Results The concentration of IL-1 (ng/L) at 2 hours in model group was gradually increased and peaked at 48 hours (4.07 ± 0.10),and then gradually decreased,while the IL-1 level in Sini decoction group peaked at 12 hours (2.98 ± 0.12) followed by a gradual decrease.IL-6 (ng/L) in model and Sini decoction groups peaked twice at 12 hours (91.39 ± 1.55,73.00 ± 2.38) and 48 hours (82.51 ± 1.49,64.68 ± 1.68) respectively.IL-10 (ng/L) in model group gradually decreased after peaking at 2 hours (86.66 ± 6.12),and that in Sini decoction decreased at 12 hours (71.61 ± 2.35) followed by an increasing tendency,and approached normal level at 48 hours (109.09 ±4.77 vs.124.01 ± 7.89,P＞0.05).TNF-α (ng/L) in model group was gradually increased and peaked at 48 hours (83.37 ±3.79),and that in Sini decoction peaked at 12 hours (48.52 ± 1.21),and decreased to normal level at 72 hours (18.59 ± 1.97 vs.15.50 ± 2.68,P＞0.05).During the course of the experiment,as compared with those of the model group,level of IL-1,IL-6,and TNF-α were significantly lower at all time points in Sini decoction group,and IL-10was significantly higher.The expression level of HLA-DR (μg/L) in model and Sini decoction groups peaked at 2 hours (4.86 ± 0.15,4.85 ± 0.17),and then gradually lowered.HLA-DR expression μg/L) at 48 hours and 72 hours in Sini decoction group was significantly lower than that in model group (48 hours:4.21 ± 0.12 vs.2.74 ± 0.16,72 hours:3.80 ± 0.09 vs.2.27 ± 0.12,both P＜0.01).Pathological study of intestinal mucosa showed that the intestinal mucosa were infiltrated significandy by inflammatory cells,and villi were damaged severely in both model group and Sini decoction group at 2 hours after LPS challenge.Infiltration of inflammatory cells in Sini decoction group was less intense after 12 hours,and the intestine villi repair was more obvious compared with model group.Conclusion Sini decoction could regulate systemic inflammatory response,and promote the repair of intestinal mucosa,the intestinal function and the immune status of septic rats.
