Effect of rhynchophylline on TGF-β1/Smad pathway for processing ventricular remodeling in spontaneously hypertensive rats

AIM: To investigate the effect of rhynchophylline (Rhy) on blood pressure, cardiac hypertrophy and myocardial fibrosis in spontaneously hypertensive rats (SHR). METHODS: Spontaneously hypertensive rats were randomly divided into model group, high dose (10 mg·kg^-1·d^-1) and low dose (2.5 mg·kg^-1·d^-1) group of rhynchophylline, captopril group (17.5 mg·kg^-1·d^-1). Wistar-Kyoto rats were used as normal control. Respectively, systolic blood pressure was measured by tail cuff every 2 weeks. After 10 weeks, heart weight index and left ventricular weight index were calculated. The myocardial hydroxyproline and plasma angiotensin Ⅱ were detected. Moreover, basic myocardial histopathological changes and myocardial collagen fibres were observed by HE staining and Masson staining, respectively. The protein expression of TGF-β₁ and Smad3 in the myocardium was measured by the methods of immunohistochemistry and Western blot. RESULTS: Compared with SHR model group, Rhy significantly reduced blood pressure (P<0.05), the levels of HYP in the myocardium (P<0.05) and the levels of AngⅡ in the plasma (P<0.01). The pathological damages of the myocardial tissues and collagen deposition were attenuated. The protein expression of TGF-β₁ and Smad3 was significantly reduced by the treatment with Rhy (P<0.01). CONCLUSION: Rhynchophylline reduces blood pressure and adjusts to improve ventricular remodeling of SHR. The mechanism may be involved in the TGF-β₁/Smad pathway and reducing AngⅡ content.     

双侧脑室引流、冲洗结合腰穿救治高血压脑出血破入全脑室患者的临床观察

目的 观察双侧脑室冲洗、引流结合腰穿治疗高血压脑出血破入全脑室的有效性和安全性.方法 将高血压脑出血破入全脑室的83例分成双管组(n=57)和单管组(n=26),双管组采用双侧脑室引流、冲洗结合腰穿的方法治疗(57例);单管组用单管引流治疗(26例),将两组治疗结果进行统计学分析和比较.结果 双管组:良好和中残35例(61.4%)、重残11例(19.3%)、植物生存2例(3.5%)、死亡9例(15.8%),单管组分别为6例(23.1%)、6例(23.1%)、1例(3.8%)、13例(50.0%),以双管组的疗效为优(P＜0.01);且双管组的病死率明显低于单管组(P＜0.01).双管组的脑脊液廓清时间为3～6(4.2±1.3)d,明显短于单管组的6～15(8.6±2.1)d(P＜0.01).结论 双管引流比单管引流更容易保持引流通畅,脑脊液廓清迅速,并发症减少,能降低病死率,提高生存质量,是一种安全、有效治疗全脑室出血的方法.     

Effects of puerarin on apelin-12, angiotensin II,NO and blood pressure in renovascular hypertensive rat

AIM: To investigate the effects of puerarin on blood pressure in renovascular hypertensive rats, and to measure puerarin-induced changes of apelin-12, angiotensin II (Ang II) and nitric oxide(NO), the factors related to development of hypertension. METHODS: Sixty-five male Sprague-Dawley rats were used, of which 8 rats were randomly selected as sham operation group, and the remaining were used to make two-kidney, one-clip model. The rats that met the criterion for Goldblatt hypertensive rat model were randomly allocated into 5 groups: high-, middle- and low-dose puerarin groups, captopril group, and model group. The drugs were administered for 6 weeks. Blood pressure was measured every 2 weeks. Six weeks after treatment, all rats were sacrificed under deep anesthesia. Blood and kidney samples were collected. The level of apelin-12 in serum and kidneys was detected by ELISA. The level of Ang II in plasma and kidneys was measured by radioimmunoassay. NO level in serum was examined by nitrate reductase assay. RESULTS: Puerarin had an antihypertensive effect in a dose-dependent manner. Marked decreases in the level of serum apelin-12 in high- and middle-dose puerarin groups were observed(P<0.01). Puerarin at low dose did not cause obvious change in the content of apelin but still reached significant level (P<0.05). As the dose of puerarin went up, the level of apelin-12 in the kidneys was gradually decreased. Puerarin at high and middle doses obviously reduced the level of AngII in plasma, while purarin at low dose did not produce any significant effects. Puerarin at high and middle doses markedly increased the level of NO in serum, but puerarin at low dose did not induce any significant changes. CONCLUSION: Puerarin has an antihypertensive effect, and its mechanism may be related to inducing the changes of apelin, Ang II and NO, and regulating the balance among those factors.     

银杏达莫联合高压氧治疗高血压脑出血术后的疗效观察

目的 观察银杏达莫注射液联合高压氧治疗微创血肿清除术后高血压脑出血的临床疗效及其安全性。方法 选取94例行微创血肿清除术的高血压脑出血患者作为研究对象,采用随机数字表法将其分为观察组及对照组。对照组给予高压氧治疗;观察组在对照组治疗的基础上另给予银杏达莫注射液治疗,两组治疗时间均为14 d。治疗后对患者疗效进行评价;治疗前后分别检测各组患者血管外周阻力(R)、动态阻力(DR)、脑血管平均流速(Vmean)和脑血管平均流量(Qmean)等脑血管功能水平,并观察各组患者NIHSS评分、Fugl-Meyer运动功能评价量表及格拉斯哥昏迷指数(GCS)评分。结果 观察组总有效率为85.1%,明显高于对照组(P<0.05)。两组患者治疗后脑血管功能指标、NIHSS、Fugl-Meyer及GCS评分均得到明显改善(P<0.05),且治疗后观察组上述指标的改善程度明显优于对照组(P<0.05)。结论 银杏达莫注射液联合高压氧治疗高血压脑出血微创血肿清除术后具有较好的疗效,值得进行深入探讨。     

NaCl plus chitosan as a dietary salt to prevent the development of hypertension in spontaneously hypertensive rats

The effect of NaCl plus 3% chitosan on the systolic blood pressure of spontaneously hypertensive rats (SHR) were evaluated and compared with NaCl plus KCl (NaCl, 49.36% + KCl 49.36%) and chitosan or NaCl treatment alone. In SHR, administration of NaCl plus chitosan (44 mM Na/day) for two months significantly decreased the systolic blood pressure greater than of NaCl plus KCl and NaCl alone. NaCl plus chitosan resulted, though not statistically significant, in decreased urinary Na⁺ excretion and decreased blood urea nitrogen levels. Urinary creatinine of NaCl plus chitosan was slightly decreased compared to 3 treated groups. Serum electrolytes levels, however, remained unchanged. The combination of NaCl and chitosan may be superior to the conventional use of NaCl plus KCl or NaCl alone in the prevention of hypertension. Even though these supplementary diets have demonstrated potential anti-hypertensive effects in the experimental animal model, further research is needed before any recommendations can be made.     

瑞士乳杆菌TUST005发酵乳ACE抑制活性的检测

【研究目的】通过对四种不同发酵剂的瑞士乳杆菌（Lactobacillus helveticus）发酵乳乳清的血管紧张素转化酶（ACE）抑制活性的体外检测和先天性高血压大鼠的体内检测。【方法】ACE抑制活性的测定根据Cushman D W等的方法进行改进。利用8周龄先天性高血压大鼠（SHR）,每天使用四种发酵乳乳清灌胃SHR大鼠,每一试验样品实验期为3 d,剂量逐渐升高,对照组饮用水。用ZH-HX-Z鼠尾无创动脉测量仪测定收缩压。【结果】瑞士乳杆菌TUST005发酵乳ACE抑制活性大于其他发酵乳ACE抑制活性,并在4 ℃下后发酵3 d具有较高的ACE抑制活性,达到45.91%。当瑞士乳杆菌TUST005发酵乳剂量15 mL/kg体重与乳清剂量为20 mL/kg体重,血压的下降和上升速度相对缓慢,维持最低血压水平时间较长为6 h,降压效果最好且与对照组相比降压值为20.2 mmHg。【结论】瑞士乳杆菌TUST005发酵乳体外检测和体内检测结果一致。     

Screening of lentiviral vectors carrying effective siRNA targeting S1P2 gene

AIM:To screen the lentiviral vector carrying siRNA with higher efficiency of suppressing the sphingosine-1-phosphate receptor 2(S1P2) gene expression in the primarily cultured corpus cavernosum smooth muscle cells of spontaneously hypertensive rats (SHR).METHODS:SHR and SD rats (n=5 each) were used for primarily culturing corpus cavernosum smooth muscle cells.The cells were randomly divided into 6 groups:SHR siRNA-1,SHR siRNA-2,SHR siRNA-3,SHR GFP,SHR control (SHR non-transfection group),and SD control (SD rat control group).Each group had 5 samples with 1.0×10⁵ cells of each sample.At 72 h after transfection (MOI=60) with lentiviral vectors carrying S1P2 siRNA into the SHR corpus cavernosum smooth muscle cells,the expression of GFP was observed under fluorescence microscope.The protein expression of S1P2,ROCK1,ROCK2 and eNOS in the corpus cavernosum smooth muscle cells,and the mRNA expression of S1P2,ROCK1 and ROCK2 were determined by by Western blot and RT-PCR.RESULTS:The transfection efficiency of the corpus cavernosum smooth muscle cells in SHR siRNA-1,SHR siRNA-2,SHR siRNA-3 and SHR GFP groups were>80%.Compared with SHR control group,the mRNA levels and the protein expression of S1P2,ROCK1 and ROCK2 in SHR GFP group showed no remarkable changes,while those in SHR siRNA-1,SHR siRNA-2,SHR siRNA-3 and SD control groups were significantly lower than those in SHR control group (P<0.05).The protein expression of eNOS in SHR siRNA-1,SHR siRNA-2,SHR siRNA-3 and SHR GFP groups were not significantly changed as compared with SHR control group,but that in SD control group was significantly higher than that in SHR control group.CONCLUSION:Three groups of siRNA lentiviral vectors targeting S1P2 inhibit the expression of S1P2 in the corpus cavernosum smooth muscle cells of SHR,and by silencing the S1P2 expression,the expression of ROCK1 and ROCK2 is inhibited.Among them,siRNA-1 has the highest inhibitory efficiency.     

Effects of aerobic exercise time on cardiovascular and renal functions of 2K1C renal vascular hypertensive rats

AIM: To explore the impact of aerobic exercise (AE) time on mean arterial pressure (MAP), sinus bradycardia, heart and kidney histological changes and oxidative damage in the two-kidney and one-clip (2K1C) hypertensive rats, and to assess the specific effects of AE time on alleviation of hypertension. METHODS: Healthy male Wistar rats (n=60) were randomly divided into sham operation (sham) group and 2K1C group. After operation, the rats in these 2 groups were divided into sham sedentary (sham+SED) group, sham exercise (sham+AE) group, 2K1C se-dentary (2K1C+SED) group and 2K1C exercise (2K1C+AE) group. The rats in sham+AE group and 2K1C+AE group were subjected to AE for 10 weeks:swimming for 1 h/d. The MAP, sinus bradycardia and the histological changes of heart and kidney in these 4 groups were tested regularly. RESULTS: Compared with 2K1C+SED group, the rats in 2K1C+AE group had significantly improved MAP and sinus bradycardia at the 4th week, with reduced collagen deposition in the myocardium and kidney, decreased level of thiobarbituric acid reactive substances (TBARS) in the left ventricle and increased catalase (CAT) activity in the left ventricle and kidney. The results of the 6th to 10th weeks showed that the differences of MAP and sinus bradycardia between the rats in 2K1C+AE group and 2K1C+SED group had gradually narrowed. The TBARS levels in the left ventricle and kidney and CAT activity in both kidneys of the rats in 2K1C+AE group were partly restored at the 8th week. The collagen deposition in the heart and kidney of the rats in AE group was reduced to the lowest level at the 10th week. CONCLUSION: Short-time (about 4 weeks) AE effectively improves the MAP and sinus bradycardia of 2K1C renal vascular hypertensive rats and attenuates the damages of the heart and kidney by regulating oxidative stress, thus improving the cardiovascular and renal functions of 2K1C renal hypertensive rats.     

Change of Gαq/11-mediated signal transduction pathway in aorta of spontaneously hypertensive rats

AIM: To investigate the changes of Gαq/11and phospholipase C(PLC) of the aorta and to evaluate the role of signal transduction pathway mediated by Gαq/11in the pathogenesis of spontaneous hypertension. METHODS: Blood pressure was measured by intubation of carotid, and the level of plasma angiotension Ⅱ was measured by radioimmunoassay. In addition, Gαq/11and PLC contents in aorta were determined by Western blot analysis. RESULTS: Arterial blood pressure was not changed in 4-week-old spontaneously hypertensive rats(SHR), but it was increased markedly in12-week-old SHR. The Gαq/11expression of aorta in 4-week-old SHR was increased by 69.2%(P<0.05) The levels of PLCβ/₃ of aorta in 4-and12-week-old SHR were increased by 66.9% and 85.1%(P<0.05), respectively, compared with their age-matched WKY rats.CONCLUSION: The up-regulation of Gαq/11-mediated signal transduction pathway of aorta may contribute to the initiation and maintenance of spontaneous hypertension.