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出血性休克和复苏后c-Jun N末端激酶的肽抑制剂调

A PEPTIDE INHIBITOR OF C-JUN N-TERMINAL KINASE MODULATES HEPATIC DAMAGE AND THE INFLAMMATORY RESPONSE AFTER HEMORRHAGIC SHOCK AND RESUSCITATION.

Hemorrhage and resuscitation (H/R) leads to phosphorylation of mitogen-activated stress kinases, an event that is associated with organ damage. Recently, a specific, cell-penetrating, protease-resistant inhibitory peptide of the mitogen-activated protein kinase c-JUN N-terminal kinase (JNK) was developed (D-JNKI-1). Here, using this peptide, we tested if inhibition of JNK protects against organ damage after H/R. Male Sprague-Dawley rats were treated with D-JNKI-1 (11 mg/kg, i.p.) or vehicle. Thirty minutes later, rats were hemorrhaged for 1 h to a MAP of 30 to 35 mmHg and then resuscitated with 60% of the shed blood and twice the shed blood volume as Ringer lactate. Tissues were harvested 2 h later. ANOVA with Tukey post hoc analysis or Kruskal-Wallis ANOVA on ranks, P < 0.05, was considered significant. c-JUN N-terminal kinase inhibition decreased serum alanine aminotransferase activity as a marker of liver injury by 70%, serum creatine kinase activity by 67%, and serum lactate dehydrogenase activity by 60% as compared with vehicle treatment. The histological tissue damage observed was blunted after D-JNKI-1 pretreatment both for necrotic and apoptotic cell death. Hepatic leukocyte infiltration and serum IL-6 levels were largely diminished after D-JNKI-1 pretreatment. The extent of oxidative stress as evaluated by immunohistochemical detection of 4-hydroxynonenal was largely abrogated after JNK inhibition. After JNK inhibition, activation of cJUN after H/R was also reduced. Hemorrhage and resuscitation induces a systemic inflammatory response and leads to end-organ damage. These changes are mediated, at least in part, by JNK. Therefore, JNK inhibition deserves further evaluation as a potential treatment option in patients after resuscitated blood loss. 本人已认领该文编译,48小时后若未提交译文,请其他战友自由认领。 A PEPTIDE INHIBITOR OF C-JUN N-TERMINAL KINASE MODULATES HEPATIC DAMAGE AND THE INFLAMMATORY RESPONSE AFTER HEMORRHAGIC SHOCK AND RESUSCITATION.
在出血性休克和复苏后c-Jun N末端激酶的肽抑制剂调节肝脏的损伤和炎症应答

Hemorrhage and resuscitation (H/R) leads to phosphorylation of mitogen-activated stress kinases, an event that is associated with organ damage.
出血和复苏后导致丝裂原活化的应激激酶的磷酸化,这是一个与器官损害有关的事件。

Recently, a specific, cell-penetrating, protease-resistant inhibitory peptide of the mitogen-activated protein kinase c-JUN N-terminal kinase (JNK) was developed (D-JNKI-1).
目前,一种特异性、细胞穿透性、蛋白酶抵抗的抑制性多肽、丝裂原活化的蛋白激酶,即c-JUN N末端激酶(JNK)正在被研究(D-JNKI-1)。

Here, using this peptide, we tested if inhibition of JNK protects against organ damage after H/R.
在这里,我们使用这种多肽,研究是否抑制JNK能保护出血和复苏后的器官损害。

Male Sprague-Dawley rats were treated with D-JNKI-1 (11 mg/kg, i.p.) or vehicle.
雄性SD大鼠给予D-JNKI-1 (11 mg/kg, 腹腔注射)或赋形剂。

Thirty minutes later, rats were hemorrhaged for 1 h to a MAP of 30 to 35 mmHg and then resuscitated with 60% of the shed blood and twice the shed blood volume as Ringer lactate.
30分钟后,损伤大鼠出血1小时达到平均主动脉压30到35 mmHg,然后给予60%的失血和2倍的失血体积的乳酸林格使大鼠复苏。

Tissues were harvested 2 h later.
2小时后取织。
ANOVA with Tukey post hoc analysis or Kruskal-Wallis ANOVA on ranks, P < 0.05, was considered significant.
采用Tukey post hoc或Kruskal-Wallis方差分析,P < 0.05表示具有显著差异。

c-JUN N-terminal kinase inhibition decreased serum alanine aminotransferase activity
as a marker of liver injury by 70%, serum creatine kinase activity by 67%, and serum lactate dehydrogenase activity by 60% as compared with vehicle treatment.
与给予赋形剂的对照组比较,抑制c-JUN N末端激酶,能降低70%的血清丙氨酸转氨酶活性,该酶是肝脏损伤的标志,67%的血清肌酸激酶活性,60%的血清乳酸脱氢酶活性。

The histological tissue damage observed was blunted after D-JNKI-1 pretreatment both for necrotic and apoptotic cell death.
在D-JNKI-1预治疗之后,不仅对坏死性而且对凋亡性细胞死亡,组织学上的组织损伤都有所缓解。

Hepatic leukocyte infiltration and serum IL-6 levels were largely diminished after D-JNKI-1 pretreatment.
在D-JNKI-1预治疗之后,肝脏白细胞浸润和血清IL-6水平明显降低。

The extent of oxidative stress as evaluated by immunohistochemical detection of 4-hydroxynonenal was largely abrogated after JNK inhibition.
通过采用免疫组织化学的方法检测4-羟基壬烯酸来评价氧化应激的程度,在抑制JNK之后,氧化应激明显减弱。

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作者:admin@医学,生命科学    2011-03-28 05:11
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