MyD88 Polymorphisms and Association with Susceptibility to Salmonella Pullorum.

Myeloid differentiation primary response gene 88 (MYD88), a universal adapter protein, plays an important role in activating the nuclear factor-κB (NF-κB) and regulating the expression of proinflammatory genes like tumor necrosis factor (TNF) and interleukin-1 (IL-1), which were highly involved in Salmonella Pullorum infection. To detect the relationship between polymorphisms of the MyD88 gene and Salmonella Pullorum disease, we screened the coding region (CDS) of the MYD88 gene by DNA pool construction and sequencing based on case-control study. Eight single nucleotide polymorphisms (SNPs) in the sequenced fragment (5 exons), 7 known loci and one novel mutation named G4810372T (SNP8), were found in the fifth exon. In addition, we found 7 nonsynonymous substitutions. The allele frequency of only one SNP, g.4810191C > T (SNP1), was significantly different (P < 0.05) between case and control groups. The genotype frequencies of SNP1 (g.4810191C > T) and SNP3 (g.4810257G > T) were of significant difference between the case and the control groups (P < 0.05). Collectively, SNPs of the MyD88 gene were significantly associated with susceptibility to Salmonella Pullorum infection, which can be used as a disease-resistant marker in chicken. These results provided a theoretical basis for future research on chicken breeding by marker-assisted selection.

[17ß-estradiol protects against injury of aortic relaxation and contraction in ovariectomized rats with insulin resistance induced by fructose].

The purpose of the present study was to investigate the effect of 17beta-estradiol (17beta-E(2)) on the structure and relaxation and contraction activity of thoracic aortas in ovariectomized rats with insulin resistance induced by fructose. Ovariectomized mature female Sprague-Dawley rats were fed with high fructose diet for 8 weeks to induce insulin resistance. Physiological dose of 17beta-E(2) (30 mug/kg) was injected subcutaneously every day for 8 weeks. Systolic blood pressure (SBP) was measured by use of tail-cuff. Serum nitric oxide (NO), estradiol (E(2)), fasting blood sugar (FBS) and fasting serum insulin (FSI) were measured respectively in each group. The insulin sensitive index (ISI) was calculated. The thoracic aortas were fixed in formalin, sliced and HE dyed. The structure of thoracic aortas, lumen breadth, media thickness, media thickness/lumen breadth ratio and media cross-section area were measured. The contraction response of thoracic aorta rings induced by L-phenylephrine (PE) and the relaxation response of thoracic aorta rings induced by ACh and sodium nitroprusside (SNP) were measured. To explore the mechanism, nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME) was used. The results obtained are as follows: (1) 17beta-E(2) protected against the effect of high fructose diet, which caused an increase in SBP, hyperinsulinemia and a decrease in ISI in ovariectomized rats. (2) The structure of thoracic aortas had no significant difference among the groups. (3) Compared with the ovariectomized group (OVX) or fructose fed group (F), serum nitric oxide was significantly reduced, the contraction response of thoracic aorta rings to PE was enhanced and the relaxation response to ACh was depressed significantly in ovariectomized+fructose fed group (OVX+F). The effect of high fructose was reversed by 17beta-E(2). After pretreatment with L-NAME, the effect of 17beta-E(2), which enhanced the relaxation response of thoracic aorta rings to ACh in ovariectomized+fructose+17beta-E(2) group (OVX+F+E(2)), was partly blocked. (4) The relaxation response of thoracic aorta rings to SNP had no significant difference among the groups. (5) The contraction response of thoracic aorta rings without endothelium to PE had no significant difference among the groups. These findings suggest that 17beta-E(2) may provide protection against the effect of high fructose diet, which causes hypertension, dysfunction of endothelial cells and insulin resistance. The mechanism of this effect of 17beta-E(2) could be partly associated with the increase of NO by NOS pathway, or associated with the decrease in the level of systolic blood pressure and serum insulin, and the improvement of insulin resistance.

[Effects of rosiglitazone on aortic function in rats with insulin resistant-hypertension].

Rosiglitazone (ROSI), thiazolidione peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activator, reduces insulin resistance in patients with type 2 diabetes (T2DM). It also improves vascular reactivity in T2DM patients and some animal models by unclear mechanisms. In order to investigate the effect of ROSI on aortic systolic and diastolic function of insulin resistant-hypertensive rats (IRHR) and the underlying mechanism, male Sprague-Dawley (SD) rats were fed with high fructose (HF) for 8 weeks to induce IRHR model. To verify IRHR model, systolic blood pressure (SBP), fasting blood sugar (FBS), fasting serum insulin (FSI) were measured respectively in each group, and insulin sensitive index (ISI) was also calculated. Subsequently, the vascular function test was performed. The thoracic aortic ring of SD rats was mounted on a bath system. The effect of rosiglitazone on the contraction elicited by L-phenylephrine (PE) and potassium chloride (KCl) and the relaxation induced by acetylcholine (ACh) and sodium nitroprusside (SNP) were measured. To explore the mechanism, nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) was used and serum nitric oxide (NO) was measured. The results obtained were as follows: (1) Rosiglitazone reduced the level of SBP, serum insulin and improved insulin resistance in IRHRs. (2) The contractive responses of thoracic aortic rings to PE and KCl were enhanced and the relaxation response to ACh was depressed significantly in the HF group, and the effect was reversed by ROSI. (3) After pretreatment with L-NAME, the relaxation response to ACh was further impaired in the HF group, this effect was partly reversed by ROSI. (4) Sodium nitroprusside (SNP)-induced vasodilator responses did not differ significantly among the groups. (5) Aortic systolic and diastolic function of the control group was not affected markedly by ROSI. (6) Compared with the control group, serum nitric oxide was significantly reduced in the HF group, but after rosiglitazone treatment it was remarkably increased. These findings suggest that ROSI can improve aortic diastolic function of insulin resistant-hypertensive rats, the mechanism of this effect might be associated with an increase in nitric oxide mediated partly by NOS pathway, a decrease in the level of blood pressure, serum insulin and the improvement of insulin resistance.