虫草素联合谷氨酰胺对LPS诱导的脓毒症大鼠炎症失衡及肝肺病理变化的影响

doi:10.13418/j.issn.1001-165x.2019.06.007

中国临床解剖学杂志 ›› 2019, Vol. 37 ›› Issue (6) : 638-643. DOI: 10.13418/j.issn.1001-165x.2019.06.007

樊晓光，　彭锦，　洪树坤，　胡国鑫，　刘健，　张志坤
赵丽姝，　王亨，　杨光虎，　乔鲁军

作者信息 +

Effects on inflammatory imbalance and pathological changes of liver and lung of cordycepin combined with glutamine in LPS-induced sepsis rats

FAN Xiao-guang, PENG Jin, HONG Shu-kun, HU Guo-xin, LIU Jian, ZHANG Zhi-kun, ZHAO Li-shu, WANG Heng, YANG Guang-hu, QIAO Lu-jun

Author information +

文章历史 +

摘要

目的　研究虫草素（cordycepin，Cop）联合谷氨酰胺（glutamine，Gln）对脂多糖（lipopolysaccharides，LPS）诱导的脓毒症大鼠炎症失衡和肝肺病理变化的影响及其可能机制。方法　将大鼠按体重随机分为5组：对照组、模型组（LPS组）、LPS+Cop组、LPS+Gln组和LPS+Cop+Gln组，腹腔注射LPS（5 mg/kg）诱导建立脓毒症大鼠模型。ELISA检测外周血中炎症因子IL-6、TNF-α、IL-1β和IL-10的含量；HE染色观察肝肺组织的病理损伤情况；TUNEL染色观察肝肺组织的细胞凋亡情况；Western blot检测肝肺组织中Caspase-3表达水平及NF-κB p65的磷酸化情况。结果　LPS+Cop组、LPS+Gln组和LPS+Cop+Gln组均能逆转LPS诱导的促炎因子（IL-6、TNF-α、IL-1β）的高表达和抗炎因子（IL-10）的低表达（P<0.05），减轻病理损伤，抑制细胞凋亡（P<0.05），降低凋亡蛋白Caspase-3高表达（P<0.05），下调NF-κB p65的磷酸化水平（P<0.05）。结论　在LPS诱导的脓毒症大鼠模型中，虫草素联合谷氨酰胺能有效改善其炎症失衡和肝肺病理变化。

Abstract

Objective To study the effects on inflammatory imbalance and pathological changes of liver and lung of cordycepin (Cop) combined with glutamine (Gln) in sepsis rats induced by lipopolysaccharide (LPS) and its possible mechanism. Methods Rats were randomly divided into five groups according to body weight: a control group, a model group (LPS group), a LPS+Cop group, a LPS+Gln group and a LPS+Cop+Gln group. The sepsis rat model was established by intraperitoneal injection of LPS (5 mg/kg). The levels of inflammatory factors IL-6, TNF-α, IL-1β and IL-10 in peripheral blood were detected by ELISA. The pathological damage of liver and lung tissue were observed by HE staining. The apoptosis rate of liver and lung tissue were detected by TUNEL staining. The expression of Caspase-3 and the phosphorylation of NF-κB p65 in liver and lung tissue were detected by Western blot. Results In the LPS+Cop group, LPS+Gln group and LPS+Cop+Gln group, reversal of high expressions of LPS-induced pro-inflammatory factors (IL-6, TNF-α, IL-1β) and low expression of anti-inflammatory factors (IL-10) could be observed (P<0.05). Also, alleviation of pathological damage, inhibition of apoptosis (P<0.05), reduction of high expression of apoptotic protein Caspase-3 (P<0.05) and down-regulation the phosphorylation level of NF-κB p65 (P<0.05) were observed. Conclusions Cordycepin combined with glutamine can effectively improve inflammation imbalance and pathological changes of liver and lung in LPS-induced sepsis rats.

导出引用

樊晓光, 彭锦, 洪树坤, 胡国鑫, 刘健, 张志坤, 赵丽姝, 王亨, 杨光虎, 乔鲁军. 虫草素联合谷氨酰胺对LPS诱导的脓毒症大鼠炎症失衡及肝肺病理变化的影响[J]. 中国临床解剖学杂志. 2019, 37(6): 638-643 https://doi.org/10.13418/j.issn.1001-165x.2019.06.007

FAN Xiao-guang, PENG Jin, HONG Shu-kun, HU Guo-xin, LIU Jian, ZHANG Zhi-kun, ZHAO Li-shu, WANG Heng, YANG Guang-hu, QIAO Lu-jun. Effects on inflammatory imbalance and pathological changes of liver and lung of cordycepin combined with glutamine in LPS-induced sepsis rats[J]. Chinese Journal of Clinical Anatomy. 2019, 37(6): 638-643 https://doi.org/10.13418/j.issn.1001-165x.2019.06.007

中图分类号： R285.5

参考文献

[1] Angus DC, van der Poll T. Severe sepsis and septic shock[J]. N Engl J Med, 2013, 369(9): 840-851.
[2] Yuki K, Murakami N. Sepsis pathophysiology and anesthetic consideration[J]. Cardiovasc Hematol Disord Drug Targets, 2015, 15(1): 57-69.
[3] Fleischmann C, Scherag A, Adhikari NK, et al. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations[J]. Am J Respir Crit Care Med, 2016, 193(3): 259-272.
[4] Cohen J, Vincent JL, Adhikari NK, et al. Sepsis: a roadmap for future research[J]. Lancet Infect Dis, 2015, 15(5): 581-614.
[5] Wu H, Liu J, Li W, et al. LncRNA-HOTAIR promotes TNF-α production in cardiomyocytes of LPS-induced sepsis mice by activating NF-κB pathway[J]. Biochem Biophys Res Commun, 2016, 471(1): 240-246.
[6] Hung YL, Fang SH, Wang SC, et al. Corylin protects LPS-induced sepsis and Attenuates LPS-induced inflammatory response[J]. Sci Rep, 2017, 7(11): 46299.
[7] Thomas RC, Bath MF, Stover CM, et al. Exploring LPS-induced sepsis in rats and mice as a model to study potential protective effects of the nociceptin/orphanin FQ system[J]. Peptides, 2014, 11(61): 56-60.
[8] Su BC, Huang HN, Lin TW, et al. Epinecidin-1 protects mice from LPS-induced endotoxemia and cecal ligation and puncture-induced polymicrobial sepsis[J]. Biochim Biophys Acta Mol Basis Dis, 2017, 1863(12): 3028-3037.
[9] Chee ME, Majumder K, Mine Y. Intervention of dietary dipeptide gamma-l-glutamyl-l-valine (γ-EV) ameliorates inflammatory response in a mouse model of LPS-induced sepsis[J]. J Agric Food Chem, 2017, 65(29): 5953-5960.
[10] Fabiani IM, Rocha SL. Evaluation of sepsis treatment with enteral glutamine in rats[J]. Rev Col Bras Cir, 2017, 44(3): 231-237.
[11] Li W, Tao S, Wu Q, et al. Glutamine reduces myocardial cell apoptosis in a rat model of sepsis by promoting expression of heat shock protein 90[J]. J Surg Res, 2017, 220(12): 247-254.
[12]Yin HY, Wei JR, Zhang R, et al. Effect of glutamine on caspase-3 mRNA and protein expression in the myocardium of rats with sepsis[J]. Am J Med Sci, 2014, 348(4): 315-318.
[13]Lei J, Wei Y, Song P, et al. Cordycepin inhibits LPS-induced acute lung injury by inhibiting inflammation and oxidative stress[J]. Eur J Pharmacol, 2018, 818: 110-114.
[14]Cao ZP, Dai D, Wei PJ, et al. Effects of cordycepin on spontaneous alternation behavior and adenosine receptors expression in hippocampus[J]. Physiol Behav, 2018, 184(2): 135-142.
[15]Hwang IH, Oh SY, Jang HJ, et al. Cordycepin promotes apoptosis in renal carcinoma cells by activating the MKK7-JNK signaling pathway through inhibition of c-FLIPL expression[J]. PLoS One, 2017, 12(10): e0186489.
[16]Newton K, Dixit VM. Signaling in innate immunity and inflammation[J]. Cold Spring Harb Perspect Biol, 2012, 4(3). pii: a006049.
[17]Davies B, Cohen J. Endotoxin removal devices for the treatment of sepsis and septic shock[J]. Lancet Infect Dis, 2011, 11(1): 65-71.
[18]Deng M, Scott MJ, Loughran P, et al. Lipopolysaccharide clearance, bacterial clearance, and systemic inflammatory responses are regulated by cell type-specific functions of TLR4 during sepsis[J]. J Immunol, 2013, 190(10): 5152-5160.
[19]Bosmann M, Ward PA. The inflammatory response in sepsis[J]. Trends Immunol, 2013, 34(3): 129-136.
[20]Okur MH, Arslan S, Aydogdu B, et al. Protective effect of cordycepin on experimental testicular ischemia/reperfusion injury in rats[J]. J Invest Surg, 2018, 31(1): 1-8.
[21]Strnad P, Tacke F, Koch A, et al. Liver-guardian, modifier and target of sepsis[J]. Nat Rev Gastroenterol Hepatol, 2017, 14(1): 55-66.
[22]Premkumar M, Saxena P, Rangegowda D, et al. Coagulation failure is associated with bleeding events and clinical outcome during systemic inflammatory response and sepsis in ACLF: an observational cohort study[J]. Liver Int, 2019, 39(4): 694-704.
[23]Jenniskens M, Langouche L, Vanwijngaerden YM, et al. Cholestatic liver (dys)function during sepsis and other critical illnesses[J]. Intensive Care Med, 2016, 42(1): 16-27.
[24]Nesseler N, Launey Y, Aninat C, et al. Clinical review: the liver in sepsis[J]. Crit Care, 2012, 16(5): 235.
[25] Zhang HB, Sun LC, Zhi LD, et al. Astilbin alleviates sepsis-induced acute lung injury by inhibiting the expression of macrophage inhibitory factor in rats[J]. Arch Pharm Res, 2017, 40(10): 1176-1185.
[26] Russell JA. Management of sepsis[J]. N Engl J Med, 2006, 355(16): 1699-1713.
[27] Kuzmich NN, Sivak KV, Chubarev VN, et al. TLR4 signaling pathway modulators as potential therapeutics in inflammation and sepsis[J]. Vaccines (Basel), 2017, 5(4): E34.