Effects of sodium butyrate acid on kidney blood flow and microvascular permeability in rats with severe scald injury
TANG Fubo1,3, GUO Jing2, ZHENG Jinguang1, BAI Xiaodong1
1. Department of Burn and Plastic Surgery, 2. Medical Department,General Hospital of the Chinese People’s Armed Police Forces,Beijing 100039,China; 3. Logistics University of Chinese People’s Armed Police Forces,Tianjin 300309,China
摘要 目的 研究丁酸钠对50%TBSA Ⅲ度烫伤大鼠肾血流量和微血管通透性的影响。方法 雄性SD大鼠48只,体重250~270 g,随机分为假烫组、烫伤组和丁酸钠组,每组16只。丁酸钠组和烫伤组分别采用100 ℃烫伤背部15 s、腹部8 s,造成50%总体表面积(TBSA)Ⅲ度烫伤,伤后立即腹腔注射丁酸钠(400 mg/kg)或等体积生理盐水。假烫组采用37 ℃温水浸泡。于伤后3 h和6 h采用多普勒血流仪测定肾脏血流量;心脏穿刺取血检测血浆肌酐(Cr);留取肾脏组织检测肾微血管通透性及肾组织含水率。结果 烫伤后3 h,烫伤组与假烫组比较,血管通透性[(9.53±1.86)μg/ml vs (7.61±0.85)μg/ml]、组织含水率[(78.72±2.07)% vs (61.71±1.86)%]、血Cr[(50.96±5.15)μmol/L vs (23.62±3.06)μmol/L]均增高,血流量明显降低[(39.18±6.28)BPU vs (140.6±21.18) BPU](均P<0.05);丁酸钠组与烫伤组比较,组织含水率[(66.95±2.26 )% vs (78.72±2.07)%]、血Cr[(33.50±6.82)μmol/L vs (50.96±5.15)μmol/L]均显著降低,血流量明显升高[(47.38±7.59) BPU vs (39.18±6.28 )BPU](均P<0.05)。烫伤后6 h,烫伤组与假烫组比较,血管通透性[(15.63±1.93)μg/ml vs (7.83±0.92)μg/ml]、组织含水率[(84.92±2.19)% vs(62.78±1.94)%]、血Cr[(87.37±10.11)μmol/L vs (24.25±2.81)μmol/L]均增高,血流量明显降低[(23.89±7.43) BPU vs (142.40±23.73)BPU](均P<0.05);丁酸钠组与烫伤组比较,血管通透性[(11.59±1.77)μg/ml vs (15.63±1.93)μg/ml]、组织含水率[(70.55±1.94)% vs (84.92±2.19)%]、血Cr[(46.00±12.35)μmol/L vs (87.37±10.11)μmol/L]均明显降低,血流量明显升高[(61.80±5.75) BPU vs (23.89±7.43) BPU](均P<0.05)。结论 丁酸钠能增加严重烫伤后肾血流量,降低肾微血管通透性和组织含水率,对严重烫伤大鼠的肾脏功能损伤有明显的保护作用。
Abstract:Objective To investigate the protective effects of sodium butyrate on kidney of rats following 50%TBSA full-thickness burns. Methods 48 SD rats, weighing 250~270g, were randomly divided into three groups: sham group, scald group, sodium butyrate group (n=16 each). Rats were subjected to 50% TBSA third-degree burns by immersing the back for 15 seconds and the abdomen for 8 seconds in 100 ℃ water. The sham group was immersed in 37 ℃ water instead. Then 1ml sodium butyrate (400 mg/kg) or 1ml normal saline was intraperitoneally injected, respectively. Renal blood flow was measured by Doppler 3 and 6 hours after injury. Blood were drawn from the heart at 3 and 6 hours after injury for measurement of plasma creatinine (Cr); then the rats were sacrificed and kidney tissues were harvested for the measurement of microvascular permeability and the changes in tissue water content. Results Compared with scald group, the level of Cr and the rate of tissue water in sodium butyrate group were significantly lower at 3 and 6 hours after scald injury(all P<0.05); the microvascular permeability in sodium butyrate group was lower than in scald group at 6 hours after injury(all P<0.05), but had no significant difference at 3 hours after injury(P>0.05). In addition, sodium butyrate significantly increased the RBF level induced by scald injury at 3 and 6 hours(all P<0.05). Conclusion Sodium butyrate has significant protective effects on kidney by increaseing the RBF and inhibiting vasopermeability and tissue edema in rats with lethal scald injury.
Fessler E B, Chibane F L, Wang Z. Potential roles of HDAC inhibitors in mitigating ischemia-induced brain damage and facilitating endogenous regeneration and recovery[J]. Curr Pharm Des, 2013,19(28):5105-5120.
[2]
Granger A, Abdullah I, Huebner F, et al. Histone deacetylase inhibition reduces myocardial ischemia-reperfusion injury in mice[J]. FASEB J, 2008, 22(10):3549-3560.
[3]
Gonzales E R, Chen H, Munuve R M, et al. Hepatoprotection and lethality rescue by histone deacetylase inhibitor valproic acid in fatal hemorrhagic shock[J]. J Trauma, 2008, 65(3):554-565.
[4]
Cianciolo C C, Skrypnyk N I, Brilli L L, et al. Histone deacetylase inhibitor enhances recovery after AKI[J]. J Am Soc Nephrol, 2013, 24(6):943-953.
Cao W, Bao C, Padalko E, Lowenstein C J. Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling[J]. J Exp Med, 2008, 205(6):1491-1503.
[7]
Zhang L, Wan J, Jiang R, et al. Protective effects of trichostatin A on liver injury in septic mice[J]. Hepatol Res, 2009, 39(9):931-938.
[8]
Zacharias N, Sailhamer E A, Li Y, et al. Histone deacetylase inhibitors prevent apoptosis following lethal hemorrhagic shock in rodent kidney cells[J]. Resuscitation, 2011, 82(1):105-109.
[9]
Lee J S, Lee G M. Effect of sodium butyrate on autophagy and apoptosis in Chinese hamster ovary cells[J]. Biotechnol Prog, 2012, 28(2):349-357.
[10]
Kato K, Kuhara A, Yoneda T, et al. Sodium butyrate inhibits the self-renewal capacity of endometrial tumor side-population cells by inducing a DNA damage response[J]. Mol Cancer Ther, 2011, 10(8):1430-1439.
[11]
Jiang W, Guo Q, Wu J, et al. Dual effects of sodium butyrate on hepatocellular carcinoma cells)[J]. Mol Biol Rep, 2012, 39(5):6235-6242.
[12]
Shin H, Lee Y S, Lee Y C. Sodium butyrate-induced DAPK-mediated apoptosis in human gastric cancer cells[J]. Oncol Rep, 2012, 27(4):1111-1115.
Gundersen B B, Blendy J A. Effects of the histone deacetylase inhibitor sodium butyrate in models of depression and anxiety[J]. Neuropharmacology, 2009, 57(1):67-74.
[15]
Chuang D M, Leng Y, Marinova Z, et al. Multiple roles of HDAC inhibition in neurodegenerative conditions[J]. Trends Neurosci, 2009, 32(11):591-601.
[16]
Kilgore M, Miller C A, Fass D M, et al. Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer’s disease[J]. Neuropsychopharmacology, 2010, 35(4):870-880.
[17]
Liang X, Wang R S, Wang F, et al. Sodium butyrate protects against severe burn-induced remote acute lung injury in rats[J]. Plos one, 2013, 8(7):191-195.
[18]
Hu X, Zhang K, Xu C. Anti-inflammatory effect of sodium butyrate preconditioning during myocardial ischemiareperfusion[J]. Exp Ther Med, 2014, 8(1):229-232.
[19]
Wang H B, Wang P Y, Wang X. Butyrate enhances intestinal epithelial barrier function via up-regulation of tight junction protein Claudin-1 transcription[J]. Dig Dis Sci,2012, 57(12): 3126-3135.
[20]
Han X, Song H, Wang Y. Sodium butyrate protects the intestinal barrier function in peritonitic mice[J]. Int J Clin Exp Med, 2015, 8(3):4000-4007.