Objective To study the effect and mechanism of atorvastatin on improving airway function of mice with chronic obstructive pulmonary disease (COPD) by inhibiting the expression of inducible nitric oxide synthase (iNOS). Methods Wild type (WT) mice were randomly divided into WT control group, WT+COPD group, WT+COPD+atorvastatin group, NC lentivirus group, NC lentivirus+COPD group, NC lentivirus+COPD+atorvastatin group, and iNOS lentivirus+COPD+atorvastatin group. Lung specific iNOS knockout (KO) mice were randomly divided into KO control group and KO+COPD group. The COPD model was established by passive inhalation of cigarette smoke. Atorvastatin (10 mg·kg–1·d–1) was given by gavage, and the negative control (NC) lentivirus or iNOS lentivirus was given by tail vein injection. The lung function indexes including peak inspiratory flow (PIF) and peak expiratory flow (PEF), the number of neutrophils (N), eosinophils (E), lymphocytes (L) and Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF), the expression levels of iNOS, endothelium nitric oxide synthase (eNOS) and neural nitric oxide synthase (nNOS) in lung tissue were measured. Results Compared with WT control group, the levels of PIF and PEF decreased, typical pathological changes of COPD appeared in lung tissue, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF, the expression of iNOS, eNOS and nNOS in lung tissue increased in WT+COPD group (all P<0.05). After atorvastatin intervention, the levels of PIF and PEF increased, the pathological changes of COPD in lung tissue ameliorated, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF, the expression of iNOS in lung tissue decreased in WT+COPD+atorvastatin group (all P<0.05). After specific knockout of iNOS in lung tissue, the levels of PIF and PEF increased, the pathological changes of COPD in lung tissue ameliorated, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF decreased in KO+COPD group (all P<0.05). After overexpression of iNOS by tail vein injection of lentiviral, the levels of PIF and PEF decreased, the pathological changes of COPD in lung tissue aggravated, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF increased in iNOS lentiviral+COPD+atorvastatin group (all P<0.05). Conclusion The effect of atorvastatin on improving airway function and inflammatory response of COPD mice is related to the inhibition of iNOS expression.
Objective To study the effect and mechanism of Xuebijing injection on sepsis-induced acute lung injury (ALI) in mice by regulating autophagy. Methods A total of 80 BALB/c male mice were randomly divided into control group, model group, Xuebijing group and Xuebijing+3-methyladenosine (3-MA) group, with 20 mice in each group. The control group received sham operation, while sepsis-induced ALI model was established in the later three groups by cecal ligation and puncture, on that basis, the Xuebijing group was given 10 mL/kg Xuebijing by intraperitoneal injection and the Xuebijing+3-MA group was given 10 mL/kg Xuebijing and 10 mg/kg autophagy inhibitor 3-mA by intraperitoneal injection. The cumulative survival rates of the four groups were observed 72 h after modeling, and the pathological changes of lung tissues, lung wet weight /dry weight ratios, inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1 β, and IL-18] contents, numbers of autophagosome, and the protein expression levels of autophagy genes [microtubule-associated protein light chain3 (LC3)-Ⅱ/LC3-Ⅰand Beclin-1] were detected. Results In the control group, the 72-hour cumulative survival rate was 100%, the lung wet weight /dry weight ratio was 3.89±0.85, the TNF-α, IL-1β, and IL-18 contents were (0.83±0.14) ng/mg, (0.74±0.15) ng/mg, and (84.51±13.25) pg/mg, respectively, the number of autophagosome was (0.41±0.09)/field, and the expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 were 0.20±0.04 and 0.17±0.03, respectively. In the model group, the lung tissue showed typical ALI pathological changes, the 72-hour cumulative survival rate (50%) was lower than that in the control group, and the lung wet weight /dry weight ratio (6.77±0.94), contents of TNF-α, IL-1β, and IL-18 [(3.15±0.76) ng/mg, (2.88±0.62) ng/mg, (274.62±45.58) pg/mg], autophagosome number [(3.14±0.55)/field], and expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 (0.69±0.09, 0.35±0.06) were higher than those in the control group (P<0.05). In the Xuebijing group, the ALI pathological changes alleviated, the 72-hour cumulative survival rate (75%), autophagosome number [(5.77±0.75)/field], and expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 (0.98±0.13, 0.62±0.08) were higher than those in the model group (P<0.05), and the lung wet weight /dry weight ratio (4.23±0.76) and contents of TNF-α, IL-1β, and IL-18 [(1.52±0.32) ng/mg, (1.29±0.30) ng/mg, (121.36±26.51) pg/mg] were lower than those in the model group (P<0.05). In the Xuebijing+3MA group, the ALI pathological changes aggravated, the 72-hour cumulative survival rate (55%), autophagosome number [(0.78±0.16)/field], and expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 (0.37±0.05, 0.32±0.05) were lower than those in the Xuebijing group (P<0.05), and the lung wet weight /dry weight ratio (6.31±0.91) and contents of TNF-α, IL-1β, and IL-18 [(2.88±0.56) ng/mg, (2.41±0.58) ng/mg, (252.35±37.65) pg/mg] were higher than those in the Xuebijing group (P<0.05). Conclusion Xuebijing injection can reduce ALI induced by sepsis in mice, and activation of autophagy is the molecular mechanism.