Protective effect and mechanism of sodium tanshinone II A sulfonate on microcirculatory disturbance of small intestine in rats with sepsis

Abstract

To explore the protective effect of sodium tanshinone IIA sulfonate (STS) on microcirculatory disturbance of small intestine in rats with sepsis, and the possible mechanism, a rat model of sepsis was induced by cecal ligation and puncture (CLP). Rats were randomly divided into 3 groups: sham operated group (S), sepsis group (CLP) and STS treatment group (STS). STS (1 mg/kg) was slowly injected through the right external jugular vein after CLP. The histopathologic changes in the intestinal tissue and changes of mesenteric microcirculation were observed. The levels of tumor necrosis factor-α (TNF-α) in the intestinal tissue were determined by using enzyme-linked immunoabsorbent assay (ELISA). The expression of intercellular adhesion molecule-1 (ICAM-1) in the intestinal tissue was detected by using immunohistochemisty and Western blot, that of nuclear factor κB (NF-κB) and tissue factor (TF) by using Western blot, and the levels of NF-κB mRNA expression by using RT-PCR respectively. The microcirculatory disturbance of the intestine was aggravated after CLP. The injury of the intestinal tissues was obviously aggravated in CLP group as compared with S group. The expression levels of NF-κB p65, ICAM-1, TF and TNF-α were upregulaed after CLP (P<0.01). STS post-treatment could ameliorate the microcirculatory disturbance, attenuate the injury of the intestinal tissues induced by CLP, and decrease the levels of NF-κB, ICAM-1, TF and TNF-α (P<0.01). It is suggested that STS can ameliorate the microcirculatory disturbance of the small intestine in rats with sepsis, and the mechanism may be associated with the inhibition of inflammatory responses and amelioration of coagulation abnormality.

Keywords

sodium tanshinone IIA sulfonate / sepsis / nuclear factor κB / tumor necrosis factor-α / intercellular adhesion molecule-1 / tissue factor

References

[1] TrzeciakS., DellingerR.P., ParrilloJ.E., et al.. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med, 2007, 49(1): 88-98

[2] MeakinsJ.L., MarshallJ.G.. Multiple organ failure syndrome. Arch Surg, 1986, 121(2): 196-208

[3] ZhuangY., ZhangY.P.. Progress in gut-derived sepsis. Int J Surg, 2007, 34(6): 403-406

[4] LiuF., ZhengZ.. The mechanisms of radix salviae miltiorrhizae in prevention of left ventricular hypertrophy in spontaneously hypertensive rats. Chin J Emerg Med (Chinese), 2004, 13(5): 322-324

[5] LinR., WangW.R., LiuJ.T., et al.. Protective effect of tanshinone A on human umbilical vein II endothelial cell injured by hydrogen peroxide and its mechanism. J Ethnopharmacol, 2006, 108(2): 217-222

[6] LiW., LiJ., AshokM., et al.. A cardiovascular drug rescues mice from lethal sepsis by selectively attenuating a late-acting proinflammatory mediator, high mobility group box 1. J Immunol, 2007, 178(6): 3856-3864

[7] XuY., FengD., WangY., et al.. Sodium tanshinone II A sulfonate protects mice from ConA-induced hepatitis via inhibiting NF-kappaB and IFN-gamma/STAT1 pathways. J Clin Immunol, 2008, 28(5): 512-519

[8] ZhouD.. Characterization of a silencer element in the human aromatase gene. Arch Biochem Biophys, 1998, 353(2): 213-220

[9] KrausJ., OschmannP., LeisS., et al.. High concentrations of Svcam-1 and sICAM-1 in the cerebrospinal fluid of patients with intracerebral hemorrhage are associated with poor outcome. J Neurot Neurosurg Psychiatry, 2002, 73(3): 346-347

[10] ParrilloJ.E., ParkerM.M., NatansonC.. Septic shock in human: advances in the understanding of prognosis, cardiovascular dysfunction and therapy. J Exp Med, 1993, 178: 951-960

[11] InceC.. Microcirculation in distress: a new resuscitation end point?. Crit Care Med, 2004, 32(9): 1963-1964

[12] InceC.. The microcirculation is the motor of sepsis. Crit Care, 2005, 9(Suppl4): S13-19

[13] NawawyA., EbrahimG.J.. Strategies for the treatment of sepsis. J Trop Pediatr, 2006, 52(3): 153-154

[14] O’HaraJ.R., BuretA.G.. Mechanisms of intestinal tight junctional disruption during infection. Front Biosc, 2008, 13: 7008-7021

[15] LiuS.F., MalikA.B.. NF-κB activation as a pathological mechanism of septic shock and inflammation. Am J Physiol Lung Cell Mol Physiol, 2006, 290: L622-645

[16] WangJ., QiaoL.F., YangG.T.. Role of Shenfu injection in rats with systemic inflammatory response syndrome. Chin J Integr Med, 2008, 14(1): 51-55

[17] BrownK.A., BrainS.D., PearsonJ.D., et al.. Neutrophils in development of multiple organ failure in sepsis. Lancet, 2006, 5(3): 157-169

[18] MatthayM.A.. Severe sepsis—a new treatment with both anticoagulant and antiinflammatory properties. N Engl J Med, 2001, 344(10): 759-762

[19] ZhaoF., ZhengS.Y., XuJ.G.. Tissue factor and sepsis. J Med Postgraduate, 2008, 21(4): 435-437

[20] JangS.I., KimH.J., KinY.J., et al.. Tanshinone II A inhibits LPS-induced NF-κB activation in RAW 264.7 cells: possible involvement of the NIK-IKK, ERK1/2, p38 and JNK Pathways. Eur J Pharmacol, 2006, 542(1–3): 1-7

[21] WangL., ZhangX., LiuL., et al.. Tanshinone II A down-regulates HMGB1, RAGE, TLR4, NF-kappaB expression, ameliorates BBB permeability and endothelial cell function, and protects rat brains against focal ischemia. Brain Res, 2010, 1321: 143-151