1.Role of acid-sensing ion channels in global cerebral ischemia-reperfusion injury in rats
Ruiqi CAO ; Xueqing LI ; Wenhao WU ; Ya LIU ; Zhenming DONG
Chinese Journal of Anesthesiology 2011;31(1):108-111
Objective To investigate the role of acid-sensing ion channels (ASICs) in global cerebral ischemia-reperfusion (I/R) injury in rats. Methods Forty-eight adult male Sprague-Dawley rats weighing 250-310 g were randomly divided into 4 groups ( n = 12 each): sham operation group (group S); global cerebral I/R group (group I/R); normal saline group (group NS) and specific ASIC blocker amiloride group (group A). Global cerebral I/R was produced by occlusion of 3 vessels ( 10 min occlusion of the bilateral common carotid arteries and basilar artery) followed by reperfusion. In group NS and A, NS 6 ml/kg and amiloride 0.6 mg/kg were injected through femoral vein immediately before reperfusion respectively. Six rats in each group were selected, the dialysate in CA1 area was collected before ischemia (baseline), immediately after ischemia and during 20 min reperfusion (once every 10 min) for determination of lactate concentrations. The left 6 rats in each group were elected at 8 h of reperfusion and the open field test and inclined plane test were peeformed to assess neurological behavior.The rats were then sacrificed and brain tissues taken for microscopic examination and brain water content was calculated. Results Compared with group S, the concentration of lactate in the dialysate and brain water content were significantly increased and neurological deficits developed in group I/R and NS (P < 0.05). Compared with group I/R, the concentration of lactate in the dialysate and brain water content were significantly decreased and neurological deficits were improved in group A ( P < 0.05 ), but no significant change in the parameters mentioned above was found in group NS ( P > 0.05). Microscopic examination showed that the damage to the brain tissues was attenuated in group A compared with group I/R. Conclusion ASICs are involved in the development of global cerebral I/R injury in rats.
2.Effect of chronic low potassium on K+ uptake rate in myocardium and skeletal muscle of rabbits
Ruiqi CAO ; Xueqing LI ; Wenhao WU ; Shuxian MA ; Yunliang YANG ; Zhenming DONG
Chinese Journal of Anesthesiology 2015;(12):1498-1500
Objective To evaluate the effect of chronic low potassium on K+uptake rate in the my?ocardium and skeletal muscle of rabbits. Methods Thirty?two adult male rabbits, aged 12-14 weeks, weighing 2?0-2?7 kg, were randomly divided into 4 groups ( n=8 each) using a random number table:normal feeding group ( group N) , low potassium feeding group ( group L) , potassium supplementation con?trol group ( group SC ) and potassium supplementation experimental group ( group SE ) . N and SC groups were given a normal diet only, and L and SE groups were fed with a low potassium diet for 15 days. Potassi?um chloride ( KCl) 0?5 mol∕L was then infused intravenously at the initial rate of 60 μmol·kg-1 ·min-1 in SE and SC groups. Blood samples were obtained from the central artery of the left ear every 5 min for meas?urement of plasma K+ concentrations. The infusion rat of KCl was then adjusted until the plasma K+concen?tration reached 5?5 mmol∕L and maintained at this level for 1 h, and then infusion was stopped. The total volume of KCl infused was recorded. The hearts and soleus muscle of animals were excised for determination of K+content. K+uptake and uptake rate were calculated. Results Compared with N group, the plasma K+concentration, and K+content in the myocardium and soleus muscle were significantly decreased in group L ( P<0?05) . Compared with SC group, the total volume of KCl infused, and K+uptake and uptake rate in the myocardium and soleus muscle were significantly increased in group SE ( P<0?05) . Conclusion Chro?nic hypokalaemia can increase K+ uptake rate in the myocardium and skeletal muscle of rabbits.
3. Correlation between CYP2C19 gene polymorphism and individualized medication in patients with ischemic stroke
Chunyong XIA ; Zuowen ZHANG ; Xiaoyan HE ; Jie LIU ; Xiaoya LI ; Qiuhong CHANG ; Lijuan QIN ; Zhenming CAO ; Ling DING
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(3):318-323
AIM: To investigate the guiding role of individualized medication adjustment based on CYP2C19 metabolic typing in the treatment of ischemic stroke with clopidogrel, and to provide reference for clinical individualized medication. METHODS: The total of 80 patients with ischemic stroke were divided into the individualized drug instruction group with gene detection (n=40) and the control group without gene detection (n=40) according to whether they received CYP2C19 gene detection. According to the metabolism of CYP2C19, the individualized medication instruction group was divided into slow metabolic type, intermediate metabolic type, fast metabolic type and ultra-fast metabolic type. Patients with fast and ultra-fast metabolites were given clopidogrel dose of 75 mg once a day. Patients with intermediate metabolic type were given double clopidogrel dose of 150 mg once a day. Patients with slow metabolism were given tigrillo dose of 90 mg twice a day or aspirin dose of 100 mg once a day. The control group received 75 mg clopidogrel once a day. All patients enrolled in the groups were followed up for 3 months by outpatients or telephone. The incidence of vascular events and mRS scale scores were compared between the two groups. RESULTS: The incidence of vascular events in the individualized drug instruction group was significantly lower than that in the control group, and the incidence of mRS score(0-1) was significantly higher than that in the control group, with statistically significant differences (P<0.05). CONCLUSION: The individualized medication for patients with ischemic stroke by CYP2C19 gene detection can significantly reduce the incidence of adverse vascular events and improve the prognosis and living ability of patients.