He Zhaohui, Zhu Zheng, Yang Xiaogang, He Huiwei, Yang Chunli
Department of Intensive Care Unit, Jiangxi Provincial People's Hospital, Nanchang 330006, Jiangxi, China.
Department of Intensive Care Unit, Central Hospital of Xinyu Iron and Steel Group Co., Ltd., Xinyu 338000, Jiangxi, China. Corresponding author: Yang Chunli, Email:
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021 May;33(5):541-545. doi: 10.3760/cma.j.cn121430-20210122-00099.
To investigate the protective effect and mechanism of celastrol in acute lung injury (ALI) of septic rats.
According to random number table, 24 male Sprague-Dawley (SD) rats were divided into control group (Con group), Sham operation group (Sham group), sepsis-induced ALI group by cecal ligation and perforation (CLP group) and celastrol intervention group (CLP+celastrol group, 2 mg/kg intraperitoneal administration 1 hour before surgery), 6 rats in each group. The abdominal aortic blood of the rats was collected for blood gas analysis 24 hours after the surgery, and then the rats were sacrificed and the lung tissues were taken to calculate the lung wet to dry weight ratio (W/D). The pathological characteristics of lung tissues were observed under light microscope and calculated the lung injury score. The protein levels of Toll-like receptor 4 (TLR4), interleukins (IL-6, IL-10), and nuclear factor-κB (NF-κB) of cytoplasm and nucleus in lung tissues were detected by enzyme linked immunosorbent assay (ELISA).
The partial arterial oxygen pressure (PaO), lung W/D ratio, lung injury score and the protein levels of inflammatory factor in lung tissues had no differences between Con group and Sham group. Compared with the Con group, PaO in the CLP group was significantly decreased [mmHg (1 mmHg = 0.133 kPa): 60.33±2.01 vs. 109.20±2.99], the lung W/D ratio and lung injury score were significantly increased (lung W/D ratio: 4.44±0.05 vs. 3.27±0.04, lung injury score: 10.67±0.42 vs. 0.50±0.22), and the protein levels of TLR4, IL-6, IL-10 and the nucleus NF-κB in the lung tissues were significantly increased [TLR4 (pg/L): 21.87±0.66 vs. 3.27±0.09, IL-6 (ng/L): 861.10±8.28 vs. 120.30±3.91, IL-10 (ng/L): 212.40±2.57 vs. 41.73±1.02, nuclear NF-κB (ng/L): 707.70±16.82 vs. 403.30±7.46], but the protein level of cytoplasm NF-κB was significantly decreased (ng/L: 213.70±8.67 vs. 408.30±8.71), with statistically significant differences (all P < 0.05). Compared with the CLP group, PaO in CLP+celastrol group was significantly increased (mmHg: 76.83±3.21 vs. 60.33±2.01), the lung W/D ratio and lung injury score were significantly decreased (lung W/D ratio: 3.82±0.03 vs. 4.44±0.05, lung injury score: 5.00±0.37 vs. 10.67±0.42), and the protein levels of TLR4, IL-6, IL-10 and nucleus NF-κB in the lung tissue were significantly decreased [TLR4 (pg/L): 7.57±0.21 vs. 21.87±0.66, IL-6 (ng/L): 380.90±6.55 vs. 861.10±8.28, nuclear NF-κB (ng/L): 533.80±9.42 vs. 707.70±16.82], and the protein level of cytoplasm NF-κB was significantly increased (ng/L: 342.70±14.96 vs. 213.70±8.67), with statistically significant differences (all P < 0.05), while the protein level of IL-10 in lung tissues had no significant difference (ng/L: 210.50±3.16 vs. 212.40±2.57, P > 0.05).
Celastrol may regulate the expression and release of inflammatory factors by inhibiting the TLR4/NF-κB pathway, thereby alleviating the ALI induced by sepsis in rats.
探讨雷公藤红素对脓毒症大鼠急性肺损伤（ALI）的保护作用及机制。
将24只雄性Sprague-Dawley（SD）大鼠按随机数字表法分为对照组（Con组）、假手术组（Sham组）、盲肠结扎穿孔致脓毒症诱导ALI组（CLP组）和雷公藤红素干预组（CLP + 雷公藤红素组，术前1小时腹腔注射2 mg/kg），每组6只。术后24小时采集大鼠腹主动脉血进行血气分析，然后处死大鼠，取肺组织计算肺湿重与干重比值（W/D）。在光镜下观察肺组织的病理特征并计算肺损伤评分。采用酶联免疫吸附测定（ELISA）法检测肺组织中Toll样受体4（TLR4）、白细胞介素（IL - 6、IL - 10）以及细胞质和细胞核中核因子 - κB（NF - κB）的蛋白水平。
Con组和Sham组之间的动脉血氧分压（PaO）、肺W/D比值、肺损伤评分及肺组织中炎症因子蛋白水平无差异。与Con组相比，CLP组PaO显著降低[mmHg（1 mmHg = 0.133 kPa）：60.33±2.01 vs. 109.20±2.99]，肺W/D比值和肺损伤评分显著升高（肺W/D比值：4.44±0.05 vs. 3.27±0.04，肺损伤评分：10.67±0.42 vs. 0.50±0.22），肺组织中TLR4、IL - 6、IL - 10及细胞核NF - κB的蛋白水平显著升高[TLR4（pg/L）：21.87±0.66 vs. 3.27±0.09，IL - 6（ng/L）：861.10±8.28 vs. 120.30±3.91，IL - 10（ng/L）：212.40±2.57 vs. 41.73±1.02，细胞核NF - κB（ng/L）：707.70±16.82 vs. 403.30±7.46]，但细胞质NF - κB蛋白水平显著降低（ng/L：(213.70±8.67) vs. (408.30±8.71)），差异均有统计学意义（均(P < 0.05)）。与CLP组相比，CLP + 雷公藤红素组PaO显著升高（mmHg：76.83±3.21 vs. 60.33±2.01），肺W/D比值和肺损伤评分显著降低（肺W/D比值：3.82±0.03 vs. 4.44±0.05，肺损伤评分：5.00±0.37 vs. 10.67±0.42），肺组织中TLR4、IL - 6、IL - 10及细胞核NF - κB的蛋白水平显著降低[TLR4（pg/L）：7.57±0.21 vs. 21.87±0.66，IL - 6（ng/L）：380.90±6.55 vs. 861.10±8.28，细胞核NF - κB（ng/L）：533.80±9.42 vs. 707.70±16.82]，细胞质NF - κB蛋白水平显著升高（ng/L：342.70±14.96 vs. 213.70±8.67），差异均有统计学意义（均(P < 0.05)），而肺组织中IL - 10蛋白水平无显著差异（ng/L：210.50±3.16 vs. 212.40±2.57，(P > 0.05)）。
雷公藤红素可能通过抑制TLR4/NF - κB通路调节炎症因子的表达与释放，从而减轻脓毒症诱导的大鼠ALI。
