Objective To investigate the effect of endogenous estrogen on myocardial L-type calcium channel α1C subunit (CACNA1C) in septic mice. Methods Female Kunming mice underwent bilateral ovarian ablation, a model of sepsis was established by cecal ligation puncture (CLP) 30 days after surgery. The experimental mice were divided into 5 groups: sepsis group (S group), ovariectomy+sepsis group (QS group), sham group (C group), ovariectomy+sham group (QC group), ovariectomy+estradiol benzoate (QE group). The expression levels of left ventricular CACNA1C were detected by real-time PCR and Western blot at 3 h, 6 h, 12 h, and 24 h after CLP. The expression and distribution of CACNA1C was detected by immunohistochemistry 3 h after CLP. Results The expression of CACNA1C in QC group was significantly higher than that in the C group, while the expression level of CACNA1C in the QE group was significantly lower than that in the QC group. At 3 h after CLP, the expression of CACNA1C in the S group was significantly higher than that in the control and other time points. At 3 h, 6 h, 12 h and 24 h after CLP, the expression of CACNA1C in the QS group was significantly lower than that in the control group, and there was no significant difference among the four time points. Conclusion The expression of CACNA1C is significantly increased after bilateral ovarian ablation. Replenishment of estradiol benzoate after lateral ovarian ablation can reverse the increase of CACNA1C. The expression of CACNA1C is transiently increased at 3 h after CLP in normal mice, while the expression of CACNA1C at each time point after CLP in bilateral ovarian-extracted mice is significantly lower than that in the control group.
Key words
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Estrogen； L- type calcium channel； CACNA1C； Sepsis
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References
[1] Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016[J]. Intensive Care Med, 2017, 43(3): 304-377.
[2] Fleischmann C, Thomas-Rueddel DO, Hartmann M, et al. Hospital incidence and mortality rates of sepsis[J]. Dtsch Arztebl Int, 2016, 113(10): 159-166.
[3] Martin L, Horst K, Chiazza F, et al. The synthetic antimicrobial peptide 19-2.5 attenuates septic cardiomyopathy and prevents down-regulation of SERCA2 in polymicrobial sepsis[J]. Sci Rep, 2016, 6: 37277.
[4] Papp R, Bett GCL, Lis A, et al. Genomic upregulation of cardiac Cav1.2alpha and NCX1 by estrogen in women [J]. Biol Sex Differ, 2017, 8(1): 26.
[5] May AK, Dossett LA, Norris PR, et al. Estradiol is associated with mortality in critically ill trauma and surgical patients[J]. Crit Care Med, 2008, 36(1): 62-68.
[6] Sakr Y, Elia C, Mascia L, et al. The influence of gender on the epidemiology of and outcome from severe sepsis[J]. Crit Care, 2013, 17(2): R50.
[7] Wu CC, Chang CY, Chang ST, et al. 17beta-estradiol accelerated renal tubule regeneration in male rats after ischemia/reperfusion-induced acute kidney injury[J]. Shock, 2016, 46(2): 158-163.
[8] Saia RS, Garcia FM, Cárnio EC. Estradiol protects female rats against sepsis induced by Enterococcus faecalis improving leukocyte bactericidal activity[J]. Steroids, 2015, 102: 17-26.
[9] Offner PJ, Moore EE, Biffl WL. Male gender is a risk factor for major infections after surgery[J]. Arch Surg, 1999, 134(9): 935-938, 938-940.
[10] Kisat M, Villegas CV, Onguti S, et al. Predictors of sepsis in moderately severely injured patients: an analysis of the National Trauma Data Bank[J]. Surg Infect (Larchmt), 2013, 14(1): 62-68.
[11] Vasudevan N, Pfaff DW. Non-genomic actions of estrogens and their interaction with genomic actions in the brain[J]. Front Neuroendocrinol, 2008, 29(2): 238-257.
[12] Johnson BD, Zheng W, Korach KS, et al. Increased expression of the cardiac L-type calcium channel in estrogen receptor-deficient mice[J]. J Gen Physiol, 1997, 110(2): 135-140.
[13] Yang X, Chen G, Papp R, et al. Oestrogen upregulates L-type Ca2+ channels via oestrogen-receptor- by a regional genomic mechanism in female rabbit hearts[J]. J Physiol, 2012, 590(3): 493-508.
[14] Marni F, Wang Y, Morishima M, et al. 17 beta-estradiol modulates expression of low-voltage-activated Ca(V)3.2 T-type calcium channel via extracellularly regulated kinase pathway in cardiomyocytes[J]. Endocrinology, 2009, 150(2): 879-888.
[15] 朱颖, 严静. 钙平衡失调在脓毒症心肌损伤中的作用[J]. 心脑血管病防治, 2014, 14(2): 149-151.
[16] Hobai IA, Edgecomb J, Labarge K, et al. Dysregulation of intracellular calcium transporters in animal models of sepsis-induced cardiomyopathy[J]. Shock, 2015, 43(1): 3-15.
