Protective Effects and Mechanisms of Shenhua Tablet (肾华片) on Toll-Like Receptors in Rat Model of Renal Ischemia-Reperfusion Injury
- 53 Downloads
To investigate the protective effects and potential mechanisms of Shenhua Tablet (肾华片, SHT) on the toll-like receptors (TLRs)-mediated signaling pathways in a rat model of kidney ischemia-reperfusion injury (IRI).
Sixty male Wistar rats were randomly divided into 5 groups: sham surgery, model control, astragaloside (150 mg•kg-1•d-1), low- and high-dose SHT (1.5 and 3.0 g•kg-1•d-1, repectively) groups. One week after drug treatment, rats underwent surgery to establish the IRI models. At 24 h and 72 h after the modeling, serum creatinine (Scr) and blood urea nitrogen (BUN) were analyzed; pathological damage were scored after periodic acid-Schiffstaining. TLR2, TLR4 and myeloid differentiation factor 88 (MyD88) protein and mRNA expressions were detected by inmmunohistochemistry, Western blot and qPCR. Tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) protein expressions were detected by enzyme linked immunosorbent assay.
Compared with the sham group, the model group exhibited severe change in renal function (Scr: 189.42±21.50, P<0.05), pathological damage (damage score: 4.50±0.55, P<0.05), and the expression levels of TLR2, TLR4, MyD88, TNF-α, IL-6 were significantly higher than other groups. Meanwhile, the levels of TLRs in model group showed upward tendency from 24 to 72 h, unparalleled with pathological and functional changes. The aforementioned parameters were alleviated to a certain extent, and, in addition to TLRs, presented the obvious downward trending from the 24 to 72 h after the intervention in the SHT and astragaloside groups relative to the model (P<0.05); in particular, the most significant mitigation of these changes was observed in the SHT-H group (P<0.05).
TLRs may be an important spot to treat and research in acute kidney injury. SHT could effectively mitigate renal injuries and promote recovery of IRI injuries through suppression of degeneration induced by up-regulation of TLR2 and TLR4 expression levels in the MyD88-dependent signaling pathway and exhibit some dose dependence.
KeywordsShenhua Tablet Chinese medicine kidney injury toll-like receptors myeloid differentiation factor 88 ischemia-reperfusion injury
Unable to display preview. Download preview PDF.
- 9.Chen XM, Chen YP, Chen J. Multicentered, randomized, controlled clinical trial on patients with IgA nephropathy of qi-yin deficiency syndrome type. Chin J Integr Tradit West Med (Chin) 2007;27:101–105.Google Scholar
- 10.Li JJ, Chen XM, Gu Y, Wei RB, Du J, Shi SZ, et al. Effect of compound Shenhua Tablet on macrophage migration inhibition factor in renal tissue of 5/6 nephrectomized rats. Chin J Integr Tradit West Med (Chin) 2005;25:150–153.Google Scholar
- 13.Daemen MA, van Veer C, Wolfs TG, Buurman WA. Ischemia/ reperfusion-induced IFN-gamma up-regulation: involvement of IL-12 and IL-18. J Immunol 1999;162:5506–5510.Google Scholar
- 22.Lam W, Bussom S, Guan F, Jiang Z, Zhang W, Gullen EA, et al. The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity. Sci Translat Med 2010;245:2841–2857.Google Scholar
- 23.Gong SG. Protection of amrinone against lung injury induced by ischemia/reperfusion in rats. Chin J Contemp Pediatr (Chin) 2007;9:233–236.Google Scholar
- 24.Zhang PJ, Jin C, Lang J. Effect of atractylodes macrocephalaon polysaccharides for reducing liver ischemia/reperfusion injury in rats after orthotopic liver autotransplantation. Chin J Integr Tradit West Med (Chin) 2010;30:1193–1196.Google Scholar