甘遂和低分子量肝素联合应用治疗重症急性胰腺炎的实验和临床研究
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摘要
背景 SAP发生后，炎症介质激活的级联放大反应，导致微循环障碍，引发全身炎症反应综合症和多器官功能衰竭。近年来发现，炎症介质、细胞因子在SAP发生发展中起重要作用，因此，抑制炎症介质、细胞因子的过度释放和改善微循环是治疗SAP的两条重要途径。我们以往的实验证明，低分子量肝素能够改善大鼠SAP的微循环和抑制SAP的炎症反应；甘遂有增强免疫、抗炎及改善胃肠道微循环的作用。本实验主要研究甘遂和低分子量肝素联合应用对SAP治疗是否有协同作用。
方法 将SD大鼠150只随机分为5组：(1)假手术组(A组)：30只；(2)重症急性胰腺炎组(B)：30只；(3)重症急性胰腺炎甘遂治疗组(C组)30只；(4)重症急性胰腺炎低分子量肝素治疗组(D组)30只；(5)：重症急性胰腺炎低分子量肝素和甘遂联合治疗组(E组)30只。各组在制成模型后2h、6h、12h、24h分别采集血标本和组织标本，进行如下指标检测：(1)血清淀粉酶；(2)血清TNF-α和IL-6水平；(3)血浆和胰腺组织TXB2／6keto-PGF1 α水平；(4)胰腺组织NF-κ B／P65和COX-2的蛋白的表达；(5)胰腺、肺、肝、肾组织HE染色光镜检查；(6)胰腺组织电镜检查；(7)各组3d的死亡率。
结果 (1)血清淀粉酶：与A组相比，B组(SAP组)血清淀粉酶水平2h就显著升高，6h达高峰，各时间点均显著高于A组(p＜0.05)；C、D、E组与B组比较，在12h、24h时间点均有显著降低(p＜0.05)，但仍高于A组(p＜0.05)。C、D、E三个治疗组在各时间点无显著差异。(2)血清TNF-α、IL-6水平：与A组相比，B组的这两个指标有显著升高；C、D、E组与B组比较，除2h外，各时间点均有显著降低(p＜0.01)，但仍高于A组(p＜0.05)，C、D、E三个治疗组在各时间点无显著差异。(3)胰腺组织、血浆TXB2、6-keto-PGF1α含量及TXB2／6-keto-PGF1α比值：TXB2含量，与A组比较，B组TXB2含量在2h就显著升高，6h达高峰，以后仍维持在较高的水平(p＜0.01)；C、D、E组TXB2含量较B组在6、12、
Background After SAP developing, the proinflammatory cytokines storm lead to Microcirculation disturbance and Systemic inflammatory response syndrome (SIRS) or Multiple organ failure( MOF). Recent researches have found that nuclear factor - kappaB(NF- κ B) and inflammatory mediators, Thromboxan2(TXA2)/Prostacyclin I2(PGI2) play important role in the development and progress of SAP.So decreasing excessive release of inflammatory mediator and improving the microcirculation of pancrease are two important ways in treatment of SAP.Our previous experimental studies had confirmed that treatment of LMWH and kansui root could improve the microcirculation disturbance and inhibit the inflammatory reaction of SAP in rats.Our ward researches have showed that kansui root had functions of immunosuppression, anti-inflammatory , improving the microcirculation of gastrointestinal tract,etc. The purpose of this present study is to investigate if there is a synergism of LMWH and kansui root in the combining treatment of SAP in rats.
Methods One hundred and fifty SD rats were randomly divided into 5 groups; (l)Sham group(A group):30 rats;(2)Severe acute pancreatitis group (B group):30 rats; (3)therapeutic group with kansui root(C group):30 rats;(4): therapeutic group with LMWH(D group):30 rats;(5) combining therapeutic group with kansui root and LMWH(E group);30 rats. The blood samples and tissue samples of each group were gathered at 2,6,12,24 hour after the operation respectively for following test:①serum amylase level;②serum tumor factor-1 α (TNF-α ) and interleukin-6(IL-6)level; ③ thromboxane-B2(TXB2) and 6-keto-prostagdin-F1 α (6-keto-PGF1 α ) level in pancreatic tissue and plasma; ④expressions of Cyclooxygenase-2(COX-2) and NF-κ B/P~(65) protein in pancreatic tissue; ⑤changes of pancreas, lung, liver, kidney tissue
方法 将SD大鼠150只随机分为5组：(1)假手术组(A组)：30只；(2)重症急性胰腺炎组(B)：30只；(3)重症急性胰腺炎甘遂治疗组(C组)30只；(4)重症急性胰腺炎低分子量肝素治疗组(D组)30只；(5)：重症急性胰腺炎低分子量肝素和甘遂联合治疗组(E组)30只。各组在制成模型后2h、6h、12h、24h分别采集血标本和组织标本，进行如下指标检测：(1)血清淀粉酶；(2)血清TNF-α和IL-6水平；(3)血浆和胰腺组织TXB2／6keto-PGF1 α水平；(4)胰腺组织NF-κ B／P65和COX-2的蛋白的表达；(5)胰腺、肺、肝、肾组织HE染色光镜检查；(6)胰腺组织电镜检查；(7)各组3d的死亡率。
结果 (1)血清淀粉酶：与A组相比，B组(SAP组)血清淀粉酶水平2h就显著升高，6h达高峰，各时间点均显著高于A组(p＜0.05)；C、D、E组与B组比较，在12h、24h时间点均有显著降低(p＜0.05)，但仍高于A组(p＜0.05)。C、D、E三个治疗组在各时间点无显著差异。(2)血清TNF-α、IL-6水平：与A组相比，B组的这两个指标有显著升高；C、D、E组与B组比较，除2h外，各时间点均有显著降低(p＜0.01)，但仍高于A组(p＜0.05)，C、D、E三个治疗组在各时间点无显著差异。(3)胰腺组织、血浆TXB2、6-keto-PGF1α含量及TXB2／6-keto-PGF1α比值：TXB2含量，与A组比较，B组TXB2含量在2h就显著升高，6h达高峰，以后仍维持在较高的水平(p＜0.01)；C、D、E组TXB2含量较B组在6、12、
Background After SAP developing, the proinflammatory cytokines storm lead to Microcirculation disturbance and Systemic inflammatory response syndrome (SIRS) or Multiple organ failure( MOF). Recent researches have found that nuclear factor - kappaB(NF- κ B) and inflammatory mediators, Thromboxan2(TXA2)/Prostacyclin I2(PGI2) play important role in the development and progress of SAP.So decreasing excessive release of inflammatory mediator and improving the microcirculation of pancrease are two important ways in treatment of SAP.Our previous experimental studies had confirmed that treatment of LMWH and kansui root could improve the microcirculation disturbance and inhibit the inflammatory reaction of SAP in rats.Our ward researches have showed that kansui root had functions of immunosuppression, anti-inflammatory , improving the microcirculation of gastrointestinal tract,etc. The purpose of this present study is to investigate if there is a synergism of LMWH and kansui root in the combining treatment of SAP in rats.
Methods One hundred and fifty SD rats were randomly divided into 5 groups; (l)Sham group(A group):30 rats;(2)Severe acute pancreatitis group (B group):30 rats; (3)therapeutic group with kansui root(C group):30 rats;(4): therapeutic group with LMWH(D group):30 rats;(5) combining therapeutic group with kansui root and LMWH(E group);30 rats. The blood samples and tissue samples of each group were gathered at 2,6,12,24 hour after the operation respectively for following test:①serum amylase level;②serum tumor factor-1 α (TNF-α ) and interleukin-6(IL-6)level; ③ thromboxane-B2(TXB2) and 6-keto-prostagdin-F1 α (6-keto-PGF1 α ) level in pancreatic tissue and plasma; ④expressions of Cyclooxygenase-2(COX-2) and NF-κ B/P~(65) protein in pancreatic tissue; ⑤changes of pancreas, lung, liver, kidney tissue
引文
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