Effects of monocrotaline-induced pulmonary hypertension on expression of Hippo signaling pathway-related molecules in rat lung

AIM:To investigate the expression of Hippo signaling pathway-related molecules in the lung tissues of the rats with pulmonary hypertension induced by monocrotaline for exploring the significance of Hippo signaling pathway in the development of pulmonary hypertension. METHODS:SD rats (n=45) were randomly divided into control group (n=15) and model group (n=30). The rats in model group was given neck subcutaneous injection of monocrota-line at 60 mg/kg to establish pulmonary hypertension model, and the rats in control group was injected with the same volume of normal saline. Four weeks later, right ventricular systolic pressure (RVSP) was measured by right cardiac catheterization, and right ventricular hypertrophy index (RVHI) and right ventricular mass index (RVMI) were calculated. The remodeling of the pulmonary arterioles was observed by HE staining, and medial thickness/external diameter (M/E%) was evaluated. The fibrosis of lung tissues was detected by Masson staining. The protein expression of Yes-associated protein (YAP), tafazzin (TAZ) and TEAD was detected by immunohistochemistry, and the protein and mRNA levels of YAP, TAZ and TEAD in lung tissues were determined by Western blot and RT-qPCR. RESULTS:Compared with control group, the vascular wall in model group was thickened significantly, the M/E% was increased (P<0.01), the pulmonary fibrosis was obvious, and the RVSP and RVHI in model group were significantly higher than those in control group (P<0.01). The immunohistochemical staining showed that the protein expression of YAP, TAZ and TEAD in the pulmonary arterioles in model group was significantly higher than that in control group. The YAP, TAZ and TEAD protein and mRNA levels in the lung tissues were also higher than those in control group (P<0.05). CONCLUSION:The activation of Hippo signaling molecules may promote the remodeling of pulmonary arterioles and further regulate the development of monocrotaline-induced pulmonary hypertension.     

虫茶联合缬沙坦治疗原发性高血压临床观察

目的 观察虫茶联合缬沙坦治疗原发性高血压的疗效。方法 将符合诊断标准的144例原发性高血压患者随机分为两组，治疗组72例给予虫茶及缬沙坦治疗，对照组72例单纯应用缬沙坦治疗。两组连续治疗4周后比较其临床疗效。结果 治疗组显效率为40.3%，总有效率为87.5%，对照组分别为25.0%和76.4%，两组疗效比较差异有统计学意义（P<0.05）。两组治疗后收缩压及舒张压比较差异有统计学意义（P<0.05），治疗组优于对照组。结论 虫茶联合缬沙坦治疗原发性高血压疗效确切。     

国医大师张学文教授治疗原发性高血压病肝热血瘀证用药规律研究

目的 应用中医传承辅助系统软件，挖掘分析张学文教授治疗原发性高血压病肝热血瘀证的用药规律。方法 收集张学文教授近5年治疗原发性高血压病肝热血瘀证的病例，采用关联规则、系统熵聚类等数据挖掘方法，分析张学文教授治疗原发性高血压病肝热血瘀证的用药经验和用药规律。结果 对筛选出的116首典型处方进行统计分析，得出处方中药物的使用频次、药物之间的关联规则、药物核心组合和新处方。结论 张学文教授诊治原发性高血压病肝热血瘀证，以天麻钩藤饮和（或）脑清通汤为基础方加减，多用平肝熄风、活血化瘀药以治标，再加补肾、安神等药以扶正，标本兼治。     

降糖降压汤对2型糖尿病合并高血压患者脂肪因子及细胞因子的影响

目的 探讨降糖降压汤对2型糖尿病合并高血压患者脂肪因子与细胞因子的影响。方法 将糖尿病合并高血压患者100例，按随机数字表法分为观察组和对照组各50例。对照组患者行常规西药降糖降压治疗，观察组患者在对照组治疗基础上，加用降糖降压汤治疗。治疗4周后，观察两组患者治疗前后血糖、血压、血脂及血浆他扎罗汀诱导基因 2（Chemerin）、血清同型半胱氨酸（Hcy）、脂联素（APN）、脑钠肽（BNP）的变化。结果 观察组总有效率为94%，对照组总有效率为76%，观察组明显高于对照组（P<0.05）；治疗后两组血糖、血压、血清三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、Chemerin、Hcy、BNP较治疗前均明显下降（P<0.05），且观察组比对照组下降更明显（P<0.05），高密度脂蛋白胆固醇（HDL-C）、APN较治疗前均有所上升（P<0.05），且观察组比对照组上升更明显（P<0.05）。结论 降糖降压汤对2型糖尿病合并高血压患者的脂肪因子及细胞因子有较好的调节功效及临床疗效，值得临床推广。     

Effect of hypercapnia on lysyl oxidase-dependent collagen cross-linking and hypoxia-induced pulmonary hypertension in rat

AIM: To investigate the effect of hypercapnia on hypoxia-induced pulmonary hypertension and the changes of lysyl oxidase (LOX) and extracellular matrix collagen cross-links in the rat. METHODS: Sprague-Dawley rats were randomly divided into 4 groups:normoxia group, hypoxia group, hypercapnia group and hypoxia+hypercapnia group. LOX activity was detected by fluorescence spectrophotometry. LOX protein expression was detected by immunohistochemistry and Western blot. The mRNA expression of LOX in the pulmonary artery was detected by real-time PCR. RESULTS: The levels of mean pulmonary artery pressure (mPAP), RV/(LV+S) and WA/TA in hypoxia group were significantly higher than those in normoxia group (P<0.01). Moreover, the levels of mPAP and RV/(LV+S) in hypoxia+hypercapnia group were significantly lower than those in hypoxia group (P<0.01). However, no significant difference of mPAP and RV/(LV+S) between hypercapnia group and normoxia group was observed. In hypoxia group, the collagen cross-links in the lung tissue was significantly higher than that in normoxia group and hypercapnia group (P<0.01). Importantly, collagen cross-links in the lung tissue of hypoxia+hypercapnia group was significantly lower than that in hypoxia group (P<0.01). There was no significant difference in collagen cross-links between hypercapnia group and normoxia group. The expression of LOX at mRNA and protein levels and its activity in the pulmonary arteries of hypoxia group were significantly increased as compared with normoxia group (P<0.01). Furthermore, the expression of LOX at mRNA and protein levels and its activity in the pulmonary arteries in hypoxia+hypercapnia group were lower than those in hypoxia group (P<0.01). CONCLUSION: Hypoxia not only up-regulates LOX but also promotes collagen cross-linking in the rat lung, which contributes to the development of pulmonary hypertension. Hypercapnia inhibits hypoxia-induced LOX expression and collagen cross-linking, therefore impairing the progress in hypoxia-induced pulmonary hypertension.     

普洱茶水提物与硝苯地平联用降压效果研究

观察普洱茶水提物对硝苯地平降压效果的影响。采用雄性SHR大鼠50只,按照平均尾动脉压随机分为模型组(M组)、硝苯地平3.1 mg·kg-1组(1/2临床剂量)(N.L组)、硝苯地平6.2 mg·kg-1组(临床剂量)(N.H组)、硝苯地平3.1 mg·kg-1+普洱茶水提物0.5 g·kg-1组(N.L+D.L组)、硝苯地平3.1 mg/kg+普洱茶水提物1.0 g·kg-1组(N.L+D.H组),每组10只,另设10只动物作为正常对照组(C组)。分组次日灌胃给予相应药物,每天2次,上午给予硝苯地平,下午给予普洱茶水提物,灌胃间隔3~4 h,每周对各组动物血压进行检测,持续4周。结果表明,大鼠给药4周后,硝苯地平6.2 mg·kg-1组大鼠尾动脉平均血压为(139?6)mm Hg(1 mm Hg=0.133 k Pa),与M组的(157?13)mm Hg比较显著降低(P0.05);N.L+D.H组大鼠尾动脉平均血压为(136?11)mm Hg,与M组的(157?13)mm Hg比较显著降低(P0.05),与硝苯地平6.2 mg·kg-1组的(139?6)mm Hg相比,降压效果相当(P0.05)。研究表明,普洱茶水提物配合硝苯地平使用,可增强硝苯地平对SHR大鼠的降压功效,其降压效果与临床剂量硝苯地平单独使用相当,且对心脏具有一定程度的保护作用。     

肺动脉高压肉鸡肺小动脉中膜5-HT量及其与肺血管重构的关系

静脉注射纤维素粒子复制肉鸡肺动脉高压模型,观察肺小动脉中膜5-羟色胺(5-HT)表达和肺小动脉管壁病理形态学变化,探讨5-HT与肺血管重构的关系。80羽科宝肉鸡分为对照组(n=30)和试验组(n=50)。20日龄时,试验组每羽鸡静脉注射0.3 mL的纤维素悬液;对照组每羽鸡静脉注射等体积生理盐水。记录肺动脉高压综合征(PHS)发病率,并分别于21、28、35、42 d从各组随机抽样,测定右心室/全心室质量比(RV/TV)、红细胞压积(PCV)、血红蛋白(Hb)、肺小动脉管壁面积/管总面积(WA/TA)、平均中膜厚度(mMTPA)和肺厚壁末梢血管百分比(TWPV%);采用免疫组化方法标记5-HT,并用病理图像分析软件检测肺小动脉5-HT的量。结果表明:试验组肉鸡PHS发病率显著高于对照组(P<0.05);RV/TV值在35、42 d时显著升高(P<0.05);PCV在28、35 d时显著升高(P<0.05);Hb值在35 d时显著升高(P<0.05);血管mMTPA、WA/TA和TWPV%在35、42 d时均显著升高(P<0.05);肺小动脉5-HT含量升高,在各时间点均差异显著(P<0.05),且5-HT含量...     

Relationship between Th17 cells infiltrated in lungs and pulmonary vascular reconstruction under hypobarric hypoxia

AIM: To investigate the changes of retinoid-related orphan receptor γt(RORγt) mRNA and interleukin-17(IL-17) protein in the lung tissue under hypobaric hypoxia, and the relationship between Th17 cells and hypoxic pulmonary vascular reconstruction. METHODS: Male BALB/c mice(n=50) were randomly divided into control group and 3 d, 7 d, 14 d and 28 d hypobaric hypoxia groups. The mice in hypobaric hypoxia groups were housed in a hypobaric hypoxia chamber(simulated altitude of 6 000 m) for 3 d, 7 d, 14 d or 28 d. The mice in control group were housed in normal pressure and oxygen environment. The hemodynamic data were recorded by cardiac catheterization. The hypertrophy of right ventricle was evaluated by the ratio of weight of the right ventricle to the weight of the left ventricle plus interventri-cular septum, and the right ventricular weight over body weight. The spleen was collected and the proportions of the Th17(CD4⁺IL-17⁺RORγt⁺) cells were detected by flow cytometry. The serum levels of IL-4, IL-6 and IL-17 and the change of IL-17 in the lung tissue were measured by ELISA. The mRNA expression of RORγt in the spleen and lung tissues was measured by RT-qPCR. RESULTS: Compared with control group, the mouse right ventricular systolic pressure, the hypertrophy index of right ventricle and the serum IL-17 level were significantly elevated in hypoxia groups, which was consistent with the results of flow cytometry. The mRNA expression of RORγt in the lung tissue was also significantly increased in 7 d, 14 d and 28 d hypoxia groups. The expression of IL-17 in the lung tissue was significantly increased in 14 d and 28 d hypoxia groups. CONCLUSION: Hypoxia promotes differentiation of Th0 cells to Th17 cells in the spleen. The Th17 cells infiltrated in the lung tissue under hypobarric hypoxia are involved in pulmonary vascular reconstruction.