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目的:研究已酮可可碱(PTX)对重度失血性休克大鼠再灌注后肝损伤的影响,并探讨其可能的作用机制.方法:48只SD大鼠随机分为4组:对照组(C组)、单纯休克组(NR组)、乳酸林格氏液组(LR组)、乳酸林格氏液联合PTX组(LRPTX组).复制重度失血性休克模型,连续检测MAP的变化.LR及LRPTX组以3倍失血量LR/LRPTX(PTX25mg/kg)液复苏.各组分别于休克前、休克1h及复苏4h时间点测谷丙转氨酶(ALT)及谷草转氨酶(AST).NR组在休克1h处死大鼠,LR组、LRPTX组及C组在复苏4h处死大鼠,取肝组织检测TNF-α、NF-κB、巨噬细胞炎性蛋白-2(MIP-2)的蛋白表达及髓过氧化物酶(MPO)活性.电镜及光镜下观察肝组织病理变化.结果:与C组比较,各组大鼠休克1hMAP(mmHg)降低(37.3±2.1,37.0±2.0,37.6±2.2vs106.0±2.6,均P<0.05),液体复苏后MAP上升,LR及LRPTX组复苏后3h及4h时间点,MAP(mmHg)下降(88.3±3.0,87.6±4.3vs105.0±2.9;69.0±2.0,66.7±2.1vs102.1±1.1,均P<0.05).与C组比较,其他各组血中AST(U/L)(142.0±8.3,144.1±7.6,147.2±8.1vs45.1±6.3;427.0±12.5,365.3±8.0vs51.1±6.3,均P<0.01)及ALT(U/L)明显升高(86.3±7.8,88.3±6.6,89.1±5.9vs53.6±6.1;342.9±4.7,280.4±9.1vs50.6±7.6,均P<0.05);肝组织TNF-α、NF-κB及MIP-2的蛋白表达明显升高,MPO活性增加(均P<0.05),肝组织病理学损伤明显;与LR组比较,LRPTX组复苏后4h血中AST及ALT明显降低(均P<0.05),TNF-α、NF-κB及MIP-2的蛋白含量明显下降,MPO活性降低(均P<0.05),肝组织病理学损伤减轻.结论:PTX通过减少TNF-α的释放,抑制NF-κB的活化,下调趋化因子的表达,减轻失血性休克再灌注后肝组织损伤.
Objective: To investigate the effects of pentoxifylline (PTX) on hepatic injury after severe hemorrhagic shock in rats and its possible mechanism.Methods: Forty eight Sprague-Dawley rats were randomly divided into 4 groups: control group (C (NR group), Ringer’s lactate group (LR group), lactated Ringer’s solution combined with PTX group (LRPTX group) .Hemorrhagic shock model was duplicated and the changes of MAP were detected continuously.LR and LRPTX group was resuscitated with 3 times the blood loss of LR / LRPTX (PTX25mg / kg) .The levels of ALT and AST were measured in each group before shock, 1 hour after shock and 4 hours after resuscitation.Results: Rats in LR group, LRPTX group and C group were sacrificed at 4h after resuscitation, and the protein expression of TNF-α, NF-κB and MIP-2 were detected by MTT and the expression of MIP-2 (MPO) activity were observed under electron microscope and light microscope pathological changes.Results: Compared with group C, the rats in each group shock 1hMAP (mmHg) decreased (37.3 ± 2.1,37.0 ± 2.0,37.6 ± 2.2vs106 (P <0.05, P <0.05). MAP increased after fluid resuscitation, MAP (mmHg) decreased at 3 h and 4 h after resuscitation in LR and LRPTX groups (88.3 ± 3.0, 87.6 ± 4.3 vs 105.0 ± 2.9, 69.0 ± 2.0,66.7 ± 2.1 vs102.1 ± 1.1, all P <0. 05) .Compared with group C, AST (U / L) in the other groups were significantly higher than those in group C (142.0 ± 8.3,144.1 ± 7.6,147.2 ± 8.1vs45.1 ± 6.3; 427.0 ± 12.5,365.3 ± 8.0vs51.1 ± 6.3, (P <0.01) and ALT (U / L) significantly increased (86.3 ± 7.8,88.3 ± 6.6,89.1 ± 5.9vs53.6 ± 6.1; 342.9 ± 4.7,280.4 ± 9.1vs50.6 ± 7.6, all P <0.05 ). The protein expressions of TNF-α, NF-κB and MIP-2 in liver tissue were significantly increased and the activity of MPO was increased (all P <0.05), and the histopathological damage was obvious. Compared with LR group, (P <0.05), while the protein levels of TNF-α, NF-κB and MIP-2 decreased significantly (all P <0.05), and the pathological damage of liver tissue decreased.Conclusion: PTX By reducing the release of TNF-α, inhibiting the activation of NF-κB, down-regulating the expression of chemokines and relieving liver injury after hemorrhagic shock-reperfusion.