Aim To determine the possibilities and mechanisms of EGFR, a receptor protein tyrosine kinase associated with many important cellular processes re-sponsible for cardiovascular remodeling in renovascular hypertensive rats. Methods 2K1C hypertensive rats were used in the present study. Blood pressure was measured with the tail-cuff method. LVMI and his-topathological changes in the cardiovascular system were analysed. EGFR expressions of aorta and myocar-dium as well as phosphorylation levels of ERK in hy-pertensive rats were detected by immunohistochemistry and Western blot analysis, respectively. Results Sys-tolic blood pressure was markedly increased 2 weeks after 2K1C surgery. Cardiovascular remodeling induced by hypertension was confirmed by elevated LVMI, pro-liferation of collagen fibers in myocardial interstitium, histopathological changes in cardiovascular system and increased IMT of thoracic aorta 6 weeks after 2 K1 C surgery. Compared with sham rats, EGFR expression in the ventricular myocardium of 2 K1 C rats was signifi-cantly increased at 6 weeks ( P<0. 05 ) , and the EG-FR/GAPDH ratio was higher in 2 K1 C rats with higher systolic blood pressure ( P < 0. 05 ) . Phosphorylation level of ERK 1/2 was upregulated correspondingly in 2 K1 C rats ( P <0. 01 ) . Increased EGFR expression was also found in aortas of 2K1C rats, particularly in tunica intima and media. Conclusion EGFR and its down-stream kinases ERK 1/2 are involved in cardio-vascular remodeling in association with the severity of hypertension in renovascular hypertensive rats.

Aims To study the effects of clenbuterol on anoxia/reoxygenation( A/R) injury in neonatal Wistar rat cardiomyocytes and to explore whether its mecha-nism is related to reperfusion injury salvage kinase ( RISK) or not. Methods The cultured primary neo-natal cardiomyocytes were randomly divided into eight groups: ①normal culture group; ②anoxia/reoxygen-ation( A/R) group;③ clenbuterol ( 1 μmol · L-1 ) +A/R;④ICI118,551(10 μmol·L-1) + clenbuterol ( 1 μmol · L-1 ) + A/R; ⑤Metoprolol ( 10μmol · L-1 ) + clenbuterol(1μmol·L-1 ) + A/R group;⑥Metoprolol ( 10 μmol · L-1 ) + A/R group; ⑦PD98059 ( 20 μmol · L-1 ) + clenbuterol ( 1 μmol · L-1 ) + A/R group;⑧ LY294002(10 μmol·L-1 ) +clenbuterol(1 μmol · L-1 ) + A/R group. Cell via-bility was determined by the conventional MTT reduc-tion assay. The content of LDH in cultured medium was measured with colorimetry. Cardiomyocyte apopto-sis was determined by Hoechst33342 . Intracellular re-active species( ROS) were monitored by the fluorescent DCFH-DA. Total ERK2 and phosphorylated ERK were detected by western blot. Results Compared with A/R group, clenbuterol significantly increased vaibility of cells, reduced LDH release, lowered the rate of apop-tosis and ROS production. When addedβ2 receptor an-tagonist ICI118 , 551 , PI3 K inhibitor LY294002 and ERK inhibitor PD98059 , the effects of clenbuterol a-bove were inhibited; but β1 receptor antagonist Meto-prolol protected the cardiomyocytes from A/R injury, as evidenced by decreased LDH release and increased cell viability. There were no synergistic effects in the combined use of clenbuterol and Metoprolol. Conclu-sion clenbuterol exerts cardioprotective effects against A/R injury by inhibiting oxidative stress and apopto-sis. The protection of clenbuterol is inhibited by ICI118 , 551 , LY294002 and PD98059 . clenbuterol protects cardiomyocytes against A/R injury via RISK pathway by activation of β2 receptor.

Oxidative stress is a hallmark in the pathogenesis of Parkinson disease (PD), which involves the selective loss of nigral dopaminergic neurons in PD. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is well known for its powerful antioxidant property and a wide range of other biological effects. In this study, we investigated the protective effect of resveratrol derived from Rhizoma Et Radix Polygoni Cuspidati and its liposomal form on the nigral cells of PD rats induced by unilateral microinjection of 6-hydroxy dopamine in the striatum. The results showed that after 14 days gavage of resveratrol and resveratrol liposome respectively (20 mg x kg(-1) WB per day), the abnormal rotational behavior of PD rats were deceased evidently, the numbers of total nigral cells, total nigral neurons and TH immuno-positive neurons were more than that of PD rats without given resveratrol or resveratrol liposome, simultaneously, the number of apoptotic nigral cells were decreased obviously. The results also showed that resveratrol and resveratrol liposome could decrease the total ROS activity, increase the total antioxidant capability of the nigral tissues. All the data indicated that resveratrol liposome performed stronger effects than resveratrol except for behavioral improvement. Our study confirmed that resveratrol derived from Rhizoma Et Radix Polygoni Cuspidati and its liposomal form could inhibit the loss of dopaminergic neurons of PD rats, the underlying mechanism may be attributed to their radical scavenging effect and antioxidant property. Due to presumably increased bioavailability, resveratrol liposome possesses the stronger therapeutic effect and may become a better clinical agent for the treatment of PD than free resveratrol.
Animals ; Antioxidants ; metabolism ; Behavior ; drug effects ; Cell Death ; drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Liposomes ; pharmacology ; Neurons ; drug effects ; metabolism ; Neuroprotective Agents ; pharmacology ; Oxidative Stress ; drug effects ; Parkinson Disease ; drug therapy ; pathology ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Stilbenes ; pharmacology ; Substantia Nigra ; drug effects ; metabolism ; pathology

AIM:To investigate the effect of non-mitogenic human acidic fibroblast growth factor(nm-haFGF)on renal ischemia-reperfusion injury in rats.METHODS:Rat renal ischemia-reperfusion(I/R)injury was produced by removing the left kidney and subsequently clamping the right renal artery for 60 min followed by reperfusion for 24 h.5 min after reperfusion.different doses of nm-haFGF and haFGF(as positive control)were injected by lingual vein.24 h later,the samples of blood,urine and kidney were collected and the contents of malondialdehyde(MDA),blood urea nitrogen(BUN),creatinine(Cr)and superoxide dismutase(SOD)activity were detected.Histopathological changes were also observed.RESULTS:In the serum,SOD activity of all the nm-haFGF groups and the haFGF group increased significantly while the content of MDA decreased dramatically compared with the model group;The content of BUN and Cr aland haFGF group rose significantly compared with the model group,while MDA decreased dramatically.Histological examination showed that nm-haFGF markedly attenuates the renal edema,brush border's defluvium and cell necrosis induced by ischemia-reperfusion.CONCLUSION:nm-haFDF could resist the renal injury induced by ischemia-reperfusion in rats.

The effects of phorbol-12,13-dibuterate (PDBu) on total sodium current (I(Na)-total), tetrodotoxin-resistant sodium current (I(Na)-TTXr), 4-AP-sensitive potassium current (I(A)) and TEA-sensitive potassium current (I(K)) in trigeminal ganglion (TG) neurons were investigated. Whole-cell patch clamp techniques were used to record ion currents in cultured TG neurons of rats. Results revealed that 0.5 micromol/L PDBu reduced the amplitude of I(Na)-total by (38.3+/-4.5)% (n=6, P<0.05), but neither the G-V curve (control: V (0.5)=-17.1+/-4.3 mV, k=7.4+/-1.3; PDBu: V (0.5)=-15.9+/-5.9 mV, k=5.9+/-1.4; n=6, P>0.05) nor the inactivation rate constant (control: 3.6+/-0.9 ms; PDBu: 3.6+/-0.8 ms; n=6, P>0.05) was altered. 0.5 micromol/L PDBu could significantly increase the amplitude of I(Na)-TTXr by (37.2+/-3.2)% (n=9, P<0.05) without affecting the G-V curve (control: V (0.5)=-14.7+/-6.0 mV, k=6.9+/- 1.4; PDBu: V (0.5)=-11.1+/-5.3 mV, k=8.1+/-1.5; n=5, P>0.05) or the inactivation rate constant (control: 4.6+/-0.6 ms; PDBu: 4.2+/-0.5 ms; n=5, P>0.05). 0.5 mumol/L PDBu inhibited I(K) by (15.6+/-5.0) % (n=16, P<0.05), and V (0.5) was significantly altered from - 4.7+/-1.4 mV to -7.9 +/-1.8 mV (n=16, P<0.05). I(A) was not significantly affected by PDBu, 0.5 mumol/L PDBu decreased I(A) by only (0.3+/-3.2)% (n=5, P>0.05). It was concluded that PDBu inhibited I(Na)-total but enhanced I(Na)-TTXr, and inhibited I(K) without affecting I(A). These data suggested that the activation of PKC pathway could exert the actions.

In order to evaluate the neuroprotective effect of Rosiglitazone Maleate (RSG) against brain ischemic injury, the effects of Rosiglitazone Maleate on the inflammation following cerebral ischemia/reperfusion were investigated. Focal cerebral ischemia was induced by the intraluminal thread for cerebral middle artery (MCA) occlusion. Rosiglitazone Maleate at concentrations of 0.5, 2 and 5 mg/kg was infused by intragastric gavage twice immediately and 2 h after MCA occlusion, respectively. The effects of Rosiglitazone Maleate on brain swelling, myeloperoxidase and interleukin-6 mRNA level in brain tissue after MCA occlusion and reperfusion were evaluated. The results showed that as compared with the model control group, RSG (0.5 mg/kg) had no significant influence on brain swelling (P>0.05), but 2 mg/kg and 5 mg/kg RSG could significantly alleviate brain swelling (P<0.05). All different doses of RSG could obviously reduce MPO activity in brain tissue after MCA occlusion and reperfusion in a dose-dependent manner. RSG (0.5 and 2 mg/kg) could decrease the expression levels of IL-6 mRNA in brain tissue after MCA occlusion and reperfusion to varying degrees (P<0.05) with the difference being significant between them. It was concluded that RSG could effectively ameliorate brain ischemic injury after 24 h MCA occlusion and inhibit the inflammatory response after ischemia-reperfusion in this model.

OBJECTIVE: To promote the development of clinical pharmacy and improve the social efficacy of ADR monitoring so as to ensure safe and rational use of drugs.METHODS: The current status of Chinese ADR monitoring system and the problems faced in the development of ADR monitoring were analyzed by means of literature review,contrasting analysis,and data reduction etc.RESULTS & CONCLUSION: There are many problems existed in the current ADR monitoring,for instance: the regulations system of ADR monitoring is unsound,the monitoring technology is weak;the cognition level of many medical workers is still very low etc.It is urgently needed to intensify propaganda on ADR monitoring,strengthen ADR monitoring,develop technological system of monitoring,set up expert database and train professional talents.

The effects of phorbol-12,13-dibuterate (PDBu) on total sodium current (INa-total), tetrodotoxin-resistant sodium current (INa-TTXr), 4-AP-sensitive potassium current (IA) and TEA-sensitive potassium current (IK) in trigeminal ganglion (TG) neurons were investigated.Whole-cell patch clamp techniques were used to record ion currents in cultured TG neurons of rats. Results revealed that 0.5 μmol/L PDBu reduced the amplitude of INa-total by (38.3±4.5)% (n=6, P＜0.05), but neither the G-V curve (control: V0.5 =-17.1±4.3 mV, k=7.4±1.3; PDBu: V0.5=-15.9±5.9 mV, k=5.9±1.4; n=6, P＞0.05) nor the inactivation rate constant (control: 3.6±0.9 ms; PDBu: 3.6±0.8 ms; n=6, P＞0.05) was altered. 0.5 μmol/L PDBu could significantly increase the amplitude of INa-TTXr by (37.2± 3.2)% (n=9, P＜0.05) without affecting the G-V curve (control: V0.5=-14.7±6.0 mV, k=6.9±1.4; PDBu: V0.5=-11.1±±5.3 mV, k=8.1±1.5; n=5, P＞0.05) or the inactivation rate constant (control: 4.6±±0.6 ms; PDBu: 4.2±0.5 ms; n=5, P＞0.05). 0.5 μmol/L PDBu inhibited IK by (15.6±5.0) % (n=16, P＜0.05), and V0.5 was significantly altered from - 4.7±1.4 mV to -7.9 ±1.8 mV (n=16, P＜0.05). IA was not significantly affected by PDBu, 0.5 μmol/L PDBu decreased IA by only (0.3±3.2)% (n=5, P＞0.05). It was concluded that PDBu inhibited INa-total but enhanced INa-TTXr, and inhibited IK without affecting IA. These data suggested that the activation of PKC pathway could exert the actions.

In order to evaluate the neuroprotective effect of Rosiglitazone Maleate (RSG) against brain ischemic injury, the effects of Rosiglitazone Maleate on the inflammation following cerebral ischemia/reperfusion were investigated. Focal cerebral ischemia was induced by the intraluminal thread for cerebral middle artery (MCA) occlusion. Rosiglitazone Maleate at concentrations of 0.5,2 and 5 mg/kg was infused by intragastric gavage twice immediately and 2 h after MCA occlusion,respectively. The effects of Rosiglitazone Maleate on brain swelling, myeloperoxidase and interleukin-6 mRNA level in brain tissue after MCA occlusion and reperfusion were evaluated. The results showed that as compared with the model control group, RSG (0.5 mg/kg) had no significant influence on brain swelling (P＞0.05), but 2 mg/kg and 5 mg/kg RSG could significantly alleviate brain swelling (P＜0.05). All different doses of RSG could obviously reduce MPO activity in brain tissue after MCA occlusion and reperfusion in a dose-dependent manner. RSG (0.5 and 2 mg/kg) could decrease the expression levels of IL-6 mRNA in brain tissue after MCA occlusion and reperfusion to varying degrees (P＜0.05) with the difference being significant between them. It was concluded that RSG could effectively ameliorate brain ischemic injury after 24 h MCA occlusion and inhibit the inflammatory response after ischemia-reperfusion in this model.

The different effects of capsaicin on I(A) and I(K) currents in pain-conduct neurons of trigeminal ganglia (TG) were investigated. In cultured TG neurons of rats, whole-cell patch clamp techniques were used to record the I(A) and I(K) before and after capsaicin perfused. Results revealed that 1 micromol/L capsaicin could inhibit the amplitude of I(A) by 48.2% (n = 10, P < 0.05), but had no inhibitory effect on I(K) (n = 7, P > 0.05). Ten micromol/L capsaicin could significantly inhibit the amplitude of I(A) by 93.2% (n = 8, P < 0.01), but only slightly inhibit the amplitude of I(K) by 13.2% (n = 7, P < 0.05). Neither 1 micromol/L nor 10 micromol/L capsaicin had effects on the active curve of I(A) and I(K). It was concluded that capsaicin could selectively inhibit the I(A) current, and this effect might involve in the analgesic mechanisms of capsaicin.