Activation of intestinal mucosal TLR4/NF-κB pathway is associated with renal damage in mice with pseudo-sterile IgA nephropathy / 细胞与分子免疫学杂志

Objective To investigate the effect of intestinal mucosal Toll-like receptor 4/nuclear factor κB (TLR4/NF-κB) signaling pathway on renal damage in pseudo-sterile IgA nephropathy (IgAN) mice. Methods C57BL/6 mice were randomly divided into experimental group (pseudosterile mouse model group), control group (IgAN mouse model group), pseudosterile mouse blank group, and normal mouse blank group. Pseudosterile mice were established by intragastric administration of quadruple antibiotics once a day for 14 days. The pseudosterile IgAN mouse model was set up by combination of oral bovine serum albumin (BSA) administration and staphylococcal enterotoxin B (SEB) injection. The pathological changes of renal tissue were observed by immunofluorescence staining and PAS staining, and the intestinal mucosa barrier damage indicators lipopolysaccharide(LPS), soluble intercellular adhesion molecule 1(sICAM-1) and D-lactate(D-LAC) were analyzed by ELISA. Biochemical analysis was used to test 24 hour urine protein, serum creatinine and blood urea nitrogen. The mRNA and protein levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor κB (NF-κB) were detected by reverse transcription PCR and Western blot analysis. Results The kidney damage of pseudosterile IgAN mice was more severe than that of IgAN mice, and the expressions of intestinal mucosal barrier damage markers (LPS, sICAM-1 and D-LAC) were significantly increased in pseudosterile IgAN mice. In addition, the expressions of TLR4, MyD88, and NF-κB level were all up-regulated in the intestinal tissues of IgAN pseudosterile mice. Conclusion Intestinal flora disturbance leads to intestinal mucosal barrier damage and induces activation of TLR4 signaling pathway to mediate renal injury in IgAN.

Relationship between parathyroid hormone level and central arterial stiffness in patients with high risk of coronary artery disease and preserved renal function / 中国实用内科杂志

Objective To study the relationship between parathyroid hormone(PTH)level and central arterial stiffness in patients with high risk of coronary artery disease(CAD) and preserved renal function.Methods Seventy-seven patients with at least one risk factor of coronary artery disease (CAD) were divided into increased arterial stiffness group(n=35) and control group(n=42),based on whether the noninvasive pulse wave analysis index of the central pulse pressure(CPP) was higher than 40mmHg or not.Coronary artery angiography was performed in all cases.Serum intact PTH,calcium,phosphor,and highly sensitive C reactive protein (hsCRP) was assessed by radioimmunoassay.Coronary angiography was also performed.Results The patients in increased arterial stiffness group were elder and had higher serum uric acid compared with those in the control group.Forty-four patients were confirmed to have CAD; CAD patients in the stiffness group (n=23) had significantly higher serum iPTH level compared with those in the control group(n=21) (P40 mmHg)after adjustment for age,BMI,hs-CRP,and male gender.Conclusion CAD patients with increased central arterial stiffness and preserved renal function have higher serum PTH level.The serum PTH level is positively correlated with central arterial stiffness,and is the independent risk factor for increased arterial stiffness.