罗格列酮对急性酒精性胃黏膜损伤的保护作用

Protective Effect of Rosiglitazone on Alcohol-induced Acute Gastric Mucosa Injury

[目的]研究过氧化物酶体增殖物液活受体γ（PPAR-γ）配体罗格列酮及奥美拉唑对酒精诱导的大鼠急性胃黏膜损伤的保护作用，并探讨其对胃黏膜环氧合酶-2（COX-2）表达的影响。[方法]50只SD大鼠，随机分为正常对照组（A组），损伤对照组（B组），奥美拉唑组（C组），罗格列酮组（D组），联合用药组（E组）。A组、B组和C组均予生理盐水5 ml/kg灌胃， C组同时予奥美拉唑30 mg/kg静脉注射，D组予罗格列酮8 mg/kg（溶于生理盐水中，相当于5 mL/kg）灌胃，E组同时予奥美拉唑（30 mg/kg ）静脉注射与罗格列酮（8 mg/kg ）灌胃。30 min后A组用18 mL/kg生理盐水灌胃，其它组大鼠均予等量56度红星二锅头白酒灌胃。通过计算胃黏膜溃疡指数（UI），免疫组织化学方法测定COX-2蛋白的表达并进行半定量测定。[结果]①B组大鼠胃黏膜损伤最重，UI明显高其他四组，差异有显著的统计学意义（P ＜0．05）；C，D，E组UI值均低于B组，但高于A组，D组UI值高于C组和E组，且组间差异均有统计学意义（ P ＜0．05）。②A组未见明显COX-2阳性产物表达；B组及C组COX-2蛋白表达均明显高于 A组，差异有统计学意义（ P ＜0．05），但两组间差异没有统计学意义（ P ＞0．05）；D组和E组COX-2蛋白表达水平均显著高于A组，但低于B组和C组，组间差异有统计学意义（均 P ＜0．05）。③各组酒精诱导胃黏膜UI与COX-2值呈正相关关系。[结论]罗格列酮对酒精诱导的急性胃黏膜损伤有保护作用，但单独应用作用不及与奥美拉唑两者联合用药。罗格列酮对急性胃黏膜损伤保护作用的机制与其抑制COX-2蛋白表达有关。

[Objective] To investigate the protective effect of peroxisome proliferators activated receptor gamma （PPAR-γ） rosigli-tazone and omeprazole on alcohol-induced acute gastric mucosa injury in rats ,and to explore the influence on the expression of COX-2 in gastric mucosa .[Methods]A total of 50 SD rats were randomly divided into normal control group （Group A ） ,injury control group （Group B） ,omeprazole group（Group C） ,rosiglitazone group（Group D） and combination treatment group（Group E） .Group A ,B and C were given normal saline 5mg/kg by lavage .Group C was given intravenous injection of omerazole 30mg/kg and rosiglitazone 8mg/kg by lavage .Group D was given rosiglitazone 8mg/kg（dissolved in normal saline and equal to 5mL/kg） by lavage .Group E was given intravenous injection of omeprazole 30mg/kg and rosiglitazone 8mg/kg by lavage .After 30min ,Group A was given normal saline 18mg/kg by lavage ,while rats in other groups were given equal 56＆#176; Hongxing Erguotou wine by lavage .Ulcer index （UI） of gastric mucosa was calculated .Immunochemistry method was used for the semi-determination of the expression of COX-2 protein .[Results]Gastric mucosa injury in Group B was the most serious .UI in Group B was obviously higher than that in other 4 groups ,and there was significant difference（ P＆lt;0 .05） .UI in Group C ,D and E were lower than that in Group B ,but higher than that in Group A .UI in Group D was higher than that in Group C and Group E ,and there was significant difference among groups （ P＆lt;0 .05） .No obvious ex-pression of COX-2 was found in Group A .The expression of COX-2 in Group B and Group C were obviously higher than that in Group A ,and there was significant difference （ P＆lt;0 .05） ,but there was no significant difference between two groups （ P＆gt;0 .05） .The ex-pression of COX-2 in Group D and Group E were markedly higher than that in Group A ,but lower than that in Group B and Group C , and there was significant difference （all P＆lt;0 .05） .UI in gastric mucosa induced by alcohol in each group was positively correlated with COX-2 .[Conclusion]Rosiglitazone has protective effect on acute gastric mucosa injury induced by alcohol .But the effect of single ros-iglitazone is inferior to rosiglitazone combined with omeprazole .The mechanism of protective effect of rosiglitazone on gastric mucosa injury is associated with the inhibition of the expression of COX-2 protein .