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

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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.	李樂輝, 楊遠征, 林潤, 等. 不同劑量血必凈注射液聯合烏司他丁注射液治療膿毒癥合并急性肺損傷的臨床觀察. 中國藥房, 2020, 31(13): 1617-1621.
4.	閆春江, 黎永琳, 李燕, 等. 血必凈注射液對膿毒癥患者血清 miR-223 及高遷移率族蛋白 B1 表達的影響. 疑難病雜志, 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.	郝軍艦, 馮智明, 才新, 等. 血必凈對盲腸結扎穿孔手術誘導的膿毒癥模型大鼠肺損傷的治療作用. 中華實驗外科雜志, 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.	蔡江紅, 楊國輝. 自噬抑制劑 3-甲基腺嘌呤在膿毒癥大鼠急性肺損傷中的作用. 醫學臨床研究, 2020, 37(1): 131-133.
9.	龔哲, 張曉旎, 李紅紅, 等. 羥基紅花黃素 A 對腦缺血再灌注后缺血半暗帶自噬活性的調節作用. 中國病理生理雜志, 2017, 33(3): 449-454.
10.	李偉文, 藍秀, 黎媛, 等. 丹酚酸 A 對脂多糖誘導人肺微血管內皮細胞線粒體自噬和細胞損傷的影響. 溫州醫科大學學報, 2018, 48(4): 267-270.
11.	任俞霏, 陳小青, 孔維宗, 等. 丹酚酸 B 對非酒精性脂肪性肝病細胞模型自噬功能的影響. 實用肝臟病雜志, 2019, 22(6): 804-807.
12.	王華, 王莉, 郭東風. 膿毒癥患者血漿微 RNA-146a 表達與患病風險、炎性因子水平及預后的相關性分析. 第二軍醫大學學報, 2020, 41(2): 135-140.
13.	孫夢, 江雪梅, 金楊, 等. 細胞外組蛋白通過激活 TWIK2-NLRP3 通路參與脂多糖誘導的肺泡巨噬細胞損傷. 中華危重病急救醫學, 2020, 32(2): 194-198.
14.	袁清紅, 劉強勝, 劉安鵬, 等. 激活大麻素 2 型受體對膿毒癥小鼠急性肺損傷的影響: 自噬在其中的作用. 中華麻醉學雜志, 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. 李樂輝, 楊遠征, 林潤, 等. 不同劑量血必凈注射液聯合烏司他丁注射液治療膿毒癥合并急性肺損傷的臨床觀察. 中國藥房, 2020, 31(13): 1617-1621.
4. 閆春江, 黎永琳, 李燕, 等. 血必凈注射液對膿毒癥患者血清 miR-223 及高遷移率族蛋白 B1 表達的影響. 疑難病雜志, 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. 郝軍艦, 馮智明, 才新, 等. 血必凈對盲腸結扎穿孔手術誘導的膿毒癥模型大鼠肺損傷的治療作用. 中華實驗外科雜志, 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. 蔡江紅, 楊國輝. 自噬抑制劑 3-甲基腺嘌呤在膿毒癥大鼠急性肺損傷中的作用. 醫學臨床研究, 2020, 37(1): 131-133.
9. 龔哲, 張曉旎, 李紅紅, 等. 羥基紅花黃素 A 對腦缺血再灌注后缺血半暗帶自噬活性的調節作用. 中國病理生理雜志, 2017, 33(3): 449-454.
10. 李偉文, 藍秀, 黎媛, 等. 丹酚酸 A 對脂多糖誘導人肺微血管內皮細胞線粒體自噬和細胞損傷的影響. 溫州醫科大學學報, 2018, 48(4): 267-270.
11. 任俞霏, 陳小青, 孔維宗, 等. 丹酚酸 B 對非酒精性脂肪性肝病細胞模型自噬功能的影響. 實用肝臟病雜志, 2019, 22(6): 804-807.
12. 王華, 王莉, 郭東風. 膿毒癥患者血漿微 RNA-146a 表達與患病風險、炎性因子水平及預后的相關性分析. 第二軍醫大學學報, 2020, 41(2): 135-140.
13. 孫夢, 江雪梅, 金楊, 等. 細胞外組蛋白通過激活 TWIK2-NLRP3 通路參與脂多糖誘導的肺泡巨噬細胞損傷. 中華危重病急救醫學, 2020, 32(2): 194-198.
14. 袁清紅, 劉強勝, 劉安鵬, 等. 激活大麻素 2 型受體對膿毒癥小鼠急性肺損傷的影響: 自噬在其中的作用. 中華麻醉學雜志, 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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