[The effects of rosiglitazone combined ceftazidime on peroxisome proliferator activated receptor γ activity and interleukin in septic rats].

Mian Zeng, Xiao-mei Huang, Wan-mei He, Hu Chen, Yu-jie Jiang
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Abstract

Objective: To observe the effects of rosiglitazone (RSG) and ceftazidime (CAZ) on peroxisome proliferator activated receptor γ (PPARγ) activity in nucleated cells and interleukin (IL-4, IL-6) levels in plasma in septic rats.

Methods: According to randomized digital table, 180 male Sprague-Dawley (SD) rats were assigned to control group, sham operation group, sepsis group, CAZ group, RSG group and combined CAZ and RSG group. Sepsis model was established by cecal ligation and puncture (CLP). Drugs were administered by intraperitoneal injection at 3-hour post-operation, once every 12-hour. The PPARγ activity in nucleated cells and IL-4, IL-6 levels in plasma were detected by enzyme linked immunosorbent assay (ELISA) at 12, 24 and 48 hours post-operation.

Results: There was no difference in PPARγ activity and levels of IL-4 and IL-6 at each time point post-operation between control group and sham operation group. Compared with control group and sham operation group, PPARγ activity [absorbance (A) value] in nucleated cells in sepsis group, where downward trend was seen as time went on, significantly reduced (0.263±0.017 vs. 0.292±0.005, 0.294±0.007, both P<0.05). PPARγ activity was significantly higher in CAZ group, RSG group and CAZ + RSG group than in sepsis group (0.282±0.008, 0.336±0.020, 0.347±0.007 vs. 0.263±0.017, all P<0.05), CAZ + RSG group>RSG group >CAZ group (both P<0.05). Plasma IL-6 and IL-4 levels were higher in sepsis group than in control group and sham operation group (IL-6: 436.77±62.28 ng/L vs. 45.11±10.42 ng/L, 42.28±7.54 ng/L; IL-4: 89.24±25.06 ng/L vs. 41.34±7.08 ng/L, 41.49±7.27 ng/L, all P<0.05) and reached peak at 24 hours and 48 hours post-operation, respectively. Compared with sepsis group, IL-6 and IL-4 levels in CAZ group, RSG group and CAZ + RSG group were significantly decreased (IL-6: 273.48±12.13 ng/L, 317.64±14.10 ng/L, 253.94±13.57 ng/L vs. 436.77±62.28 ng/L; IL-4: 59.12±7.03 ng/L, 68.37±8.28 ng/L, 53.81±8.34 ng/L vs. 89.24±25.06 ng/L, all P<0.05), CAZ + RSG group < CAZ group < RSG group (all P<0.05).

Conclusion: In septic rats, PPARγ activity in nucleated cells was decreased. On the basis of effective antibiotic treatment, RSG might play a role in improving PPARγ activity in nucleated cells and reducing the levels of inflammation mediators and anti-inflammatory in plasma.

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罗格列酮联合头孢他啶对脓毒症大鼠过氧化物酶体增殖物激活受体γ活性和白细胞介素的影响。
目的:观察罗格列酮(RSG)和头孢他啶(CAZ)对脓毒症大鼠有核细胞过氧化物酶体增殖物激活受体γ (PPARγ)活性和血浆白细胞介素(IL-4、IL-6)水平的影响。方法:将180只雄性SD大鼠按随机数字表法分为对照组、假手术组、脓毒症组、CAZ组、RSG组和CAZ与RSG联合组。采用盲肠结扎穿刺法(CLP)建立脓毒症模型。术后3小时腹腔注射给药,每12小时1次。术后12、24、48 h采用酶联免疫吸附法(ELISA)检测有核细胞中PPARγ活性及血浆中IL-4、IL-6水平。结果:假手术组与对照组术后各时间点PPARγ活性及IL-4、IL-6水平差异无统计学意义。与对照组和假手术组比较,脓毒症组有核细胞中PPARγ活性[吸光(A)值]随时间的延长呈下降趋势,明显降低(0.263±0.017 vs. 0.292±0.005,0.294±0.007,均为PRSG组>CAZ组)。结论:脓毒症大鼠有核细胞中PPARγ活性降低。在有效的抗生素治疗基础上,RSG可能具有提高有核细胞PPARγ活性,降低血浆中炎症介质和抗炎物质水平的作用。
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