Effect and mechanism of Xuebijing injection on sepsis-induced acute lung injury in mice_West China Medical Journal

Authors：

WANG Jia ¹ ,  GAO Hengbo ² , LIN Xuerong ¹ , LUO Xiaoyu ¹ , CHEN Lijun ¹ , HAN Shuchi ¹

1. Emergency Department, the First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075000, P. R. China;
2. Emergency Department, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P. R. China;

Corresponding author：

GAO Hengbo, Email: hengbogao@sina.com

Keywords：

Sepsis; Acute lung injury; Xuebijing; Autophagy; Inflammatory response; Mouse

DOI：

10.7507/1002-0179.202109177

Video：

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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.

Citation： WANG Jia, GAO Hengbo, LIN Xuerong, LUO Xiaoyu, CHEN Lijun, HAN Shuchi. Effect and mechanism of Xuebijing injection on sepsis-induced acute lung injury in mice. West China Medical Journal, 2021, 36(11): 1533-1538. doi: 10.7507/1002-0179.202109177 Copy

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2.	Irving SY, Daly B, Verger J, et al. The association of nutrition status expressed as body mass index Z score with outcomes in children with severe sepsis: a secondary analysis from the sepsis prevalence, outcomes, and therapies (SPROUT) study. Crit Care Med, 2018, 46(11): e1029-e1039.
3.	李乐辉, 杨远征, 林润, 等. 不同剂量血必净注射液联合乌司他丁注射液治疗脓毒症合并急性肺损伤的临床观察. 中国药房, 2020, 31(13): 1617-1621.
4.	闫春江, 黎永琳, 李燕, 等. 血必净注射液对脓毒症患者血清 miR-223 及高迁移率族蛋白 B1 表达的影响. 疑难病杂志, 2019, 18(3): 243-246.
5.	Zhang SK, Zhuo YZ, Li CX, et al. Xuebijing injection and resolvin D1 synergize regulate leukocyte adhesion and improve survival rate in mice with sepsis-induced lung injury. Chin J Integr Med, 2018, 24(4): 272-277.
6.	郝军舰, 冯智明, 才新, 等. 血必净对盲肠结扎穿孔手术诱导的脓毒症模型大鼠肺损伤的治疗作用. 中华实验外科杂志, 2019, 36(6): 1141.
7.	Zhao H, Chen H, Xiaoyin M, et al. Autophagy activation improves lung injury and inflammation in sepsis. Inflammation, 2019, 42(2): 426-439.
8.	蔡江红, 杨国辉. 自噬抑制剂 3-甲基腺嘌呤在脓毒症大鼠急性肺损伤中的作用. 医学临床研究, 2020, 37(1): 131-133.
9.	龚哲, 张晓旎, 李红红, 等. 羟基红花黄素 A 对脑缺血再灌注后缺血半暗带自噬活性的调节作用. 中国病理生理杂志, 2017, 33(3): 449-454.
10.	李伟文, 蓝秀, 黎媛, 等. 丹酚酸 A 对脂多糖诱导人肺微血管内皮细胞线粒体自噬和细胞损伤的影响. 温州医科大学学报, 2018, 48(4): 267-270.
11.	任俞霏, 陈小青, 孔维宗, 等. 丹酚酸 B 对非酒精性脂肪性肝病细胞模型自噬功能的影响. 实用肝脏病杂志, 2019, 22(6): 804-807.
12.	王华, 王莉, 郭东风. 脓毒症患者血浆微 RNA-146a 表达与患病风险、炎性因子水平及预后的相关性分析. 第二军医大学学报, 2020, 41(2): 135-140.
13.	孙梦, 江雪梅, 金杨, 等. 细胞外组蛋白通过激活 TWIK2-NLRP3 通路参与脂多糖诱导的肺泡巨噬细胞损伤. 中华危重病急救医学, 2020, 32(2): 194-198.
14.	袁清红, 刘强胜, 刘安鹏, 等. 激活大麻素 2 型受体对脓毒症小鼠急性肺损伤的影响: 自噬在其中的作用. 中华麻醉学杂志, 2018, 38(12): 1509-1512.
15.	Guo QQ, Wang SS, Zhang SS, et al. ATM-CHK2-Beclin 1 axis promotes autophagy to maintain ROS homeostasis under oxidative stress. EMBO J, 2020, 39(10): e103111.
16.	Abd El Maksoud AI, Elebeedy D, Abass NH, et al. Methylomic changes of autophagy-related genes by legionella effector Lpg2936 in infected macrophages. Front Cell Dev Biol, 2019, 7(7): 390.
17.	Wang Z, Li Y, Yang X, et al. Protective effects of rapamycin induced autophagy on CLP septic mice. Comp Immunol Microbiol Infect Dis, 2019, 64: 47-52.

1. Thakkar RK, Weiss SL, Fitzgerald JC, et al. Risk factors for mortality in pediatric postsurgical versus medical severe sepsis. J Surg Res, 2019, 242: 100-110.
2. Irving SY, Daly B, Verger J, et al. The association of nutrition status expressed as body mass index Z score with outcomes in children with severe sepsis: a secondary analysis from the sepsis prevalence, outcomes, and therapies (SPROUT) study. Crit Care Med, 2018, 46(11): e1029-e1039.
3. 李乐辉, 杨远征, 林润, 等. 不同剂量血必净注射液联合乌司他丁注射液治疗脓毒症合并急性肺损伤的临床观察. 中国药房, 2020, 31(13): 1617-1621.
4. 闫春江, 黎永琳, 李燕, 等. 血必净注射液对脓毒症患者血清 miR-223 及高迁移率族蛋白 B1 表达的影响. 疑难病杂志, 2019, 18(3): 243-246.
5. Zhang SK, Zhuo YZ, Li CX, et al. Xuebijing injection and resolvin D1 synergize regulate leukocyte adhesion and improve survival rate in mice with sepsis-induced lung injury. Chin J Integr Med, 2018, 24(4): 272-277.
6. 郝军舰, 冯智明, 才新, 等. 血必净对盲肠结扎穿孔手术诱导的脓毒症模型大鼠肺损伤的治疗作用. 中华实验外科杂志, 2019, 36(6): 1141.
7. Zhao H, Chen H, Xiaoyin M, et al. Autophagy activation improves lung injury and inflammation in sepsis. Inflammation, 2019, 42(2): 426-439.
8. 蔡江红, 杨国辉. 自噬抑制剂 3-甲基腺嘌呤在脓毒症大鼠急性肺损伤中的作用. 医学临床研究, 2020, 37(1): 131-133.
9. 龚哲, 张晓旎, 李红红, 等. 羟基红花黄素 A 对脑缺血再灌注后缺血半暗带自噬活性的调节作用. 中国病理生理杂志, 2017, 33(3): 449-454.
10. 李伟文, 蓝秀, 黎媛, 等. 丹酚酸 A 对脂多糖诱导人肺微血管内皮细胞线粒体自噬和细胞损伤的影响. 温州医科大学学报, 2018, 48(4): 267-270.
11. 任俞霏, 陈小青, 孔维宗, 等. 丹酚酸 B 对非酒精性脂肪性肝病细胞模型自噬功能的影响. 实用肝脏病杂志, 2019, 22(6): 804-807.
12. 王华, 王莉, 郭东风. 脓毒症患者血浆微 RNA-146a 表达与患病风险、炎性因子水平及预后的相关性分析. 第二军医大学学报, 2020, 41(2): 135-140.
13. 孙梦, 江雪梅, 金杨, 等. 细胞外组蛋白通过激活 TWIK2-NLRP3 通路参与脂多糖诱导的肺泡巨噬细胞损伤. 中华危重病急救医学, 2020, 32(2): 194-198.
14. 袁清红, 刘强胜, 刘安鹏, 等. 激活大麻素 2 型受体对脓毒症小鼠急性肺损伤的影响: 自噬在其中的作用. 中华麻醉学杂志, 2018, 38(12): 1509-1512.
15. Guo QQ, Wang SS, Zhang SS, et al. ATM-CHK2-Beclin 1 axis promotes autophagy to maintain ROS homeostasis under oxidative stress. EMBO J, 2020, 39(10): e103111.
16. Abd El Maksoud AI, Elebeedy D, Abass NH, et al. Methylomic changes of autophagy-related genes by legionella effector Lpg2936 in infected macrophages. Front Cell Dev Biol, 2019, 7(7): 390.
17. Wang Z, Li Y, Yang X, et al. Protective effects of rapamycin induced autophagy on CLP septic mice. Comp Immunol Microbiol Infect Dis, 2019, 64: 47-52.

West China Medical Journal

Effect and mechanism of Xuebijing injection on sepsis-induced acute lung injury in mice

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