[ ABSTRACT] AIM:To investigate the role of the Notch pathway in Toll-like receptor 4 ( TLR4 )-mediated in-flammatory response in renal ischemia reperfusion injury ( IRI) in rats.METHODS: A total of 75 male sprague-Dawley rats were randomly divided into sham operation group , IRI group and DAPT treatment group .Blood samples and the kid-neys were obtained at 6 h, 12 h, 24 h, 48 h and 72 h after reperfusion .The concentrations of blood urea nitrogen ( BUN) and serum creatinine (Scr) were measured.The serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) were detected by ELISA, and the expression of Notch1, TLR4 and NF-κB p65 in the renal tissues was assessed by im-munohistochemistry and Western blot .RESULTS: The serum levels of BUN, Scr, TNF-αand IL-6 in IRI group were markedly increased as compared with sham group (P<0.05).The protein levels of Notch1, TLR4 and NF-κB p65 in re-nal tubular epithelial cells in IRI group was significantly enhanced as compared with sham group ( P<0.05 ) .In DAPT group, the serum levels of BUN, Scr, TNF-αand IL-6 were significantly reduced compared with IRI group (P<0.05), and the protein levels of Notch1, TLR4 and NF-κB p65 were apparently less than those in IRI group (P<0.05).CON-CLUSION:Significant changes of renal function , a rise of serum inflammatory factor including TNF-αand IL-6 and en-hanced expression of Notch 1, TLR4 and NF-κB p65 in the renal tissue occurred in the rats with IRI .γ-Secretase inhibitor DAPT attenuates TLR4-mediated inflammatory response in the renal IRI through the inhibition of Notch 1 and down-regula-tion of NF-κB.

[ ABSTRACT] AIM:To investigate the expression of calprotectin ( CALP) in the rats with renal ischemia-reperfu-sion injury ( IRI) .METHODS:Male Sprague-Dawley rats were randomly divided into sham operation and IRI group ( n=25 in each group) .Blood samples and the kidneys were obtained at 6 h, 12 h, 24 h, 48 h and 72 h after reperfusion.The pathological changes of the kidneys were observed.The serum concentrations of blood urea nitrogen ( BUN) and serum cre-atinine (SCr) were measured.The serum levels of CALP, tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) were detected by ELISA, and the expression of CALP, Toll-like receptor 4 ( TLR4) and NF-κB p65 in the renal tissues were de-termined by the methods of immunohistochemistry and Western blot.RESULTS: Different serial ischemia changes were observed in the renal tissues, mainly in the renal tubular epithelial cells and the mesenchyma, with the infiltration of in-flammatory cells.The serum levels of BUN, SCr, CALP, TNF-αand IL-6 in IRI group were markedly increased as com-pared with sham group (P<0.05).The protein expression of CALP, TLR4 and NF-κB p65 in the renal tubular epithelial cells in IRI group was greatly enhanced in comparison with that in sham group ( P<0.05) .CONCLUSION:The serum concentrations of CALP, TNF-αand IL-6, and the protein expression levels of CALP, TLR4 and NF-κB p65 in the renal tissue are significantly increased in the rats with IRI, suggesting that calprotectin plays an important role in the inflamma-tion in rats with IRI.

OBJECTIVE: To determine the effect of trimetazidine on cardiac function and exercise tolerance in primary hypertension patients with type 2 diabetic. METHODS: In this randomized, double-blind, placebo-controlled prospective study, 60 primary hypertensive patients with diabetic were equally assigned into two groups, patients received trimetazidine (20 mg, 3 times a day) or placebo for 1 year. Echocardiography, cardiopulmonary exercise testing were performed; and the plasma N terminal pro B type natriuretic peptide (NT-ProBNP), hr-CRP, TNF-α, angiotensin Ⅱ and endothelin concentration were determined before and after treatment. RESULTS: In trimetazidine group, the left ventricular mass index, the mitral flow velocity E wave to A wave ratio (E/A), the peak early diastolic velocity (V) to late diastolic velocity (V) ratio (V/V) and the peak systolic velocity (Vs) were significantly improved, the plasma NT-ProBNP level was significantly decreased, and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were significantly increased (all <0.05); plasma concentration of hr-CRP, TNF-α, angiotensin Ⅱ and endothelin were significantly reduced after trimetazidine treatment, compared with baseline (all <0.05) and with placebo (all <0.05). There were no significant differences in any of above parameters after treatment in placebo group (all >0.05). No severe adverse reaction was observed in both groups. CONCLUSIONS For patients with both hypertension and diabetes, trimetazidine can improve cardiac function and increase exercise tolerance.
Diabetes Complications ; complications ; Diabetes Mellitus ; drug therapy ; Double-Blind Method ; Exercise Tolerance ; drug effects ; Heart ; drug effects ; Humans ; Hypertension ; complications ; drug therapy ; Natriuretic Peptide, Brain ; blood ; Prospective Studies ; Treatment Outcome ; Trimetazidine ; pharmacology ; therapeutic use ; Vasodilator Agents ; pharmacology ; therapeutic use