TJ0711, a novel vasodilatory ß-blocker, protects SHR rats against hypertension induced renal injury.

Previous studies suggested that ß-blockers with adjunctive α1-blocking activities warrant renoprotective function other than the therapeutic effect on hypertension. The current report is designed to dissect the role of TJ0711, a novel ß-blocker with a 1:1 ratio for the ß1/α1 blocking activities, in renoprotection in SHR rats. It was noted that TJ0711 possesses similar potency for control of blood pressure as that of Carvedilol. However, TJ0711 is much more potent in terms of protecting SHR rats against hypertension induced renal injury. Specifically, SHR rats treated with 20mg/kg/day of TJ0711 manifested significantly lower levels for urine albumin and total protein. In line with these result, TJ0711 treated rats displayed much less severe pathological changes in the kidneys. Mechanistic studies revealed that TJ0711 improves kidney perfusion during the course of hypertensive insult by enhancing eNOS expression through suppressing inflammatory cytokine secretion. TJ0711 also attenuates Vasohibin-1 expression to prevent HIF-1α from signal-induced degradation, and by which it promotes HO-1 expression to protect SHR rats against oxidative stress induced by hypertension in the kidneys. Together, our data suggest that TJ0711 possesses higher potency for renoprotection while manifesting the similar effect on hypertension therapy as Carvedilol.

[The detection of flavonoids glycosides from ginkgo biloba based on spectrofluorimetry].

Flavonoids glycosides from ginkgo are widely applied in pharmaceutical, food, daily necessities and other areas due to their variety of biological activities. To overcome the shortcoming of current methods of time wasting, complex operation and expensive costs, an accuracy, low costs and fast determination method was established for flavonoids glycosides from ginkgo. According to the principle that flavonoids can form fluorescent chelate with Al3+, the detection condition was explored with rutin as standard. The results showed that the fluorimetric intensy of chelate of rutin with Al3+ would be stabilized and achieve maximum with lambda(ex) = 400 nm and lambda(em) = 520 nm, in Al (NO3)3-(HAc-NaAc) reaction system for 1 500 s with pH 3.6. The linear regression equation y = 29.92x + 36.49 (R2 = 0.986) was deduced with the concentration of rutin and fluorescence intensy, and the linear range 1.8 x 10(-6) -3.2 x 10(-5) mol x L(-1). Flavonoids glycosides of cell suspension cultures from ginkgo biloba was detected by this method. The recovery experiments were also carried out with the average recovery rate of 101.3%. The advantages of high sensitivity, reproducibility, simple operation, and low costs were showed, indicating its good prospects.

[Effect of kurarinone on renal tubular epithelial cell-mesenchyma trans-differentiation in rats with renal interstitial fibrosis].

OBJECTIVE: To study the effect of Kurarinone on renal tubular epithelial cell-mesenchyma (ECM) trans-differentiation in rats with renal interstitial fibrosis and to explore its possible mechanisms. METHODS: The rat model of renal interstitial fibrosis was established by unilateral ureteral obstruction (UUO). Sprague-Dawley male rats were randomly divided into 3 groups, the sham-operated group, the UUO group and the Kurarinone treated group (KTG). Rats in the KTG were intraperitoneally injected with Kurarinone 100 mg/kg daily after modeling. Five rats of each group were killed respectively at day 7, 14 and 21 after UUO. The serum levels of blood urea nitrogen (BUN), serum creatinine (SCr), total protein (TP) and albumin (ALB), 24-h urinary protein excretion in rats were measured. Pathological changes of renal tissue were observed by PAS and Masson stain. The expression of transforming growth factor beta1 (TGF-beta1), Smad3, alpha-smooth muscle actin (alpha-SMA) and collagen I (Col I) in kidney were determined with immunohistochemistry. And the expressions of TGF-beta1 and alpha-SMA mRNA in renal tissue were determined using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The expression of TGF-beta1, Smad3, alpha-SMA and Col I in the KTG was significantly decreased as compared with that in the UUO group respectively, and the degree of tubular damage and renal interstitial fibrosis was also ameliorated more obviously in the KTG. The TGF-beta1 and alpha-SMA mRNA expressions in KTG were significantly lower than those in the UUO group determined at the corresponding time points (P < 0.05). CONCLUSION: Kurarinone could down-regulate the expression of TGF-beta1 and Col I, inhibit EC-M trans-differentiation, suppress the activation and proliferation of myofibroblast. The probable pathway may be by way of down-regulating Smad3 expression to interfere its induction on intercellular signal transduction and consequently ameliorate renal interstitial fibrosis.