BML-111通过调节NLRP3炎症激活ROS产生来介导慢性阻塞性肺疾病的抗炎作用

BML-111 mediates the anti-inflammatory effect of chronic obstructive pulmonary disease by regulating nucleotide binding oligomerization domain-like receptor 3 inflammatory activation reactive oxygen species production

目的探讨脂氧素受体激动剂(BML-111)通过调节核苷酸结合寡聚化结构域样受体3(NLRP3)炎症激活活性氧(ROS)产生来介导COPD的对于抗炎的作用的影响。方法SPF级雄性小鼠32只随机数字法分成4组,正常组、COPD模型组、BML-111低剂量组、BML-111高剂量组,每组8只,应用脂多糖和烟熏的方式建模,观察小鼠的COPD情况,通过HE染色观察小鼠的炎性细胞浸润情况,通过Western blot检测NLRP3、1L-1β、转化生长因子β(TGF-β)的蛋白的表达情况,通过支气管肺泡灌洗液(BALF)制备观察不同的细胞计数情况,氧化应激测定超氧化物歧化酶(SOD)和丙二醛(MDA)的活性。结果正常组建模前后差异无统计学意义(P=0.719),COPD模型组、BML-111低剂量组、BML-111高剂量建模后体质量明显低于建模前的体质量(P=0.027);COPD模型组的NLRP3、1L-1β、TGF-β的蛋白表达明显高于正常组(P=0.009),BML-111低剂量组的NLRP3、1L-1β、TGF-β的蛋白表达低于COPD模型组(P=0.032),BML-111高剂量组的NLRP3、1L-1β、TGF-β的蛋白表达显著低于COPD模型组(P=0.006);模型组中的白细胞计数明显高于正常组(P=0.017),BML-111高剂量组淋巴细胞计数显著低于模型组(P=0.036);COPD模型组的SOD的活性明显低于正常组(P=0.011),BML-111低剂量组的SOD的活性高于COPD模型组(P=0.028),BML-111高剂量组的SOD的活性显著高于COPD模型组(P=0.009);COPD模型组的MDA的活性明显高于正常组(P=0.013),BML-111低剂量组的MDA的活性低于COPD模型组(P=0.026),BML-111高剂量组的MDA的活性显著低于COPD模型组(P=0.005)。结论BML-111可以通过抑制NLRP3炎性小体的活化介导ROS产生来抵抗COPD的炎症发生。

Objective To investigate the lipoxygen receptor agonist(BML-111)mediated by the regulation of nucleotide binding oligomerization domain-like receptor 3(NLRP3)inflammation activated reactive oxygen species(ROS)to mediate The effect of COPD on the anti-inflammatory effect.Methods A total of 32 SPF male mice were randomly divided into 4 groups,the normal group,the COPD model group,the BML-111 low-dose group,and the BML-111 high-dose group,8 mice per group.Modeling with lipopolysaccharide and smoking method,observation of COPD in mice,observation of inflammatory cell infiltration in mice by HE staining,detection of NLRP3,1L-1β,transforming growth factorβ(TGF-β)protein expression,observe the different cell counts through the preparation of bronchoalveolar lavage fluid(BALF),and determine the activity of superoxide dismutase(SOD)and malondialdehyde(MDA)by oxidative stress.Results There was no significant difference between the normal group before and after modeling(P=0.719).The weight of the COPD model group,BML-111 low-dose group,BML-111 after high-dose modeling was significantly lower than the body weight before modeling(P=0.027).NLRP3,1L-1β,TGF-βprotein expression in the COPD model group was significantly higher than that in the normal group(P=0.009),NLRP3,1L-1βin the low dose group of BML-111,TGF-βprotein expression is lower than the COPD model group(P=0.032),BML-111 high-dose group NLRP3,1L-1β,TGF-βprotein expression is significantly lower than the COPD model group(P=0.006).The white blood cell count in the model group was significantly higher than that in the normal group(P=0.017),and the lymphocyte count in the BML-111 high-dose group was significantly lower than that in the model group(P=0.036).The SOD activity of the COPD model group was significantly lower than that of the normal group(P=0.011),The activity of SOD in the low-dose group of BML-111 was higher than that in the COPD model group(P=0.028),the activity of SOD in the high-dose BML-111 group was significantly higher than that in the COPD model group(P=0.009).The activity of MDA in the COPD model group was significantly higher than that in the normal group(P=0.013),and the MDA activity in the low-dose BML-111 group was lower than that in the COPD model group(P=0.026).The activity of MDA in BML-111 high-dose group was significantly lower than that in COPD model group(P=0.005).Conclusions Bml-111 can inhibit the inflammation of COPD by inhibiting the activation of NLRP3 inflammatory bodies and mediating ROS production.