益气化瘀汤辅助治疗对慢性心力衰竭患者微血管损伤和心室重构及代谢重构的影响

目的 探讨自拟益气化瘀汤辅助治疗慢性心力衰竭(chronic heart failure,CHF)气虚血瘀证患者的临床疗效及可能的作用机制分析。 方法 选择2017年5月—2019年2月杭州市中医院收治的CHF气虚血瘀证患者120例,采用随机数字表法随机分为对照组和治疗组,各60例,均接受常规抗心衰药物治疗,对照组加服曲美他嗪,治疗组在对照组的基础上加用益气化瘀汤,连续治疗6个月。比较2组患者中医证候疗效、血管内皮功能参数、心室重构参数、能量代谢重构参数的差异。 结果 治疗6个月后,治疗组患者总有效率为80.00%,高于对照组的58.33%(χ2=6.604,P=0.010)。治疗后治疗组和对照组患者内皮素-1、血管紧张素Ⅱ、醛固酮、左心室质量指数、左心室收缩末周向室壁应力、心肌能量消耗值分别为(68.42±21.95)ng/L、(77.53±35.28)pg/mL、(197.38±71.84)pg/mL、(125.69±21.84)g/m2、(130.75±18.93)kdyne/cm2、(92.67±9.83)kcal/min和(82.68±22.53)ng/L、(101.14±36.11)pg/mL、(262.33±95.83)pg/mL、(131.47±25.36)g/m2、(144.58±21.63)kdyne/cm2、(101.28±11.45)kcal/min,治疗组患者上述指标均低于对照组(均P<0.05)。 结论 自拟益气化瘀汤辅助曲美他嗪治疗慢性心力衰竭气虚血瘀证患者可抑制微血管损伤、心室重构和能量代谢重构进程,纠正患者的病理状态和中医症状,以达到“对症”“对证”治疗的目的。      

Xuezhikang(血脂康) Reduced Renal Cell Apoptosis in Streptozocin-Induced Diabetic Rats through Regulation of Bcl-2 Family

Objective: To investigate the effect of Xuezhikang(血脂康, XZK) on renal cell apoptosis in diabetic rats and the possible mechanism. Methods: Sixty-six rats were randomly divided into 3 groups: the normal, model and XZK groups. In each group, the rats were further randomly divided into 3-month and 6-month subgroups, respectively. Diabetes of rats was induced by a single intraperitoneal injection of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received gastric perfusion of XZK(1200 mg/kg body weight) everyday for 3 or 6 months, while rats in the normal and model groups received equal volume of saline. Twenty-four hours' urine was collected for urinary albumin excretion(UAE) measurement. Periodic acid-Schiff(PAS) and Masson's trichrome staining were used for saccharides and collagen detection. Cell apoptosis of renal cortex was investigated by Td T-mediated d UTP nick end labeling(TUNEL) staining. Bax and Bcl-2 expressions were detected by immunohistochemistry and Western blot, respectively. Cytochrome C(Cyt C) and caspase-9 concentration were detected by Western blot. Results: Compared with the model group, XZK treatment could significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to the suppression of Bax/Bcl-2 ratio at 3 and 6 months(P0.05 or P0.01). Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides and Masson's trichromestained collagen to different extent. Conclusions: Renal cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic pathway might be involved. XZK treatment could attenuate pathological changes in diabetic kidney and reduce renal cell apoptosis, probably via the suppression of Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase-9 activation.     

自噬在晚期糖基化终产物诱导的内皮细胞凋亡中的作用

目的: 研究晚期糖基化终产物(AGEs)对人脐静脉内皮细胞(HUVECs)自噬水平的影响并探讨自噬在AGEs诱导的内皮细胞凋亡中的作用。方法: 用AGEs处理HUVECs,相同条件牛血清白蛋白处理为对照组,Western blotting检测相应蛋白表达的变化,电镜观察细胞自噬体的出现,流式细胞术检测细胞凋亡,MTT比色法测定细胞活性。结果: AGEs处理HUVECs后,自噬相关蛋白LC3-Ⅱ的表达显著上调并呈时间和浓度依赖性,电镜观察到细胞胞浆内自噬体数量增加;与对照组比较,AGEs处理组内皮细胞凋亡率增加,活性下降,自噬抑制剂3-甲基腺嘌呤预处理的AGEs组细胞活性较AGEs组进一步下降,凋亡率继续增加。AGEs处理HUVECs后,蛋白激酶B(Akt)和哺乳动物雷帕霉素靶蛋白(mTOR)的磷酸化水平也明显下调, Akt激活剂胰岛素样生长因子1预处理后,Akt的磷酸化水平增加,自噬相关蛋白LC3-Ⅱ的增高表达被抑制。结论: AGEs通过PI3K/Akt/mTOR介导的信号通路诱导HUVECs自噬水平升高。自噬在AGEs诱导的内皮细胞凋亡中对细胞起保护作用。     

血脂康对糖尿病大鼠心功能不全及肌浆网Ca~（2＋）-ATP酶的影响

目的：研究血脂康对糖尿病大鼠心功能不全及心肌细胞肌浆网Ca2＋-ATP酶（SERCA2a）的影响。方法：8周龄SD雄性大鼠腹腔注射链脲佐菌素造模成功后随机分为3组,血脂康组、糖尿病模型组和正常对照组,共喂养12周。颈动脉插管行血流动力学检查,并测定血总胆固醇（TC）、甘油三脂（TG）、高密度脂蛋白（HDL）及低密度脂蛋白（LDL）;提取左心室组织,Western-blotting分析各组大鼠心肌细胞SERCA2a表达。结果：模型组大鼠LDL水平显著高于正常组,HDL水平较正常组降低;血脂康组血脂水平较模型组变化不明显。模型组心室峰压（LVSP）、左心室内压上升最大速率（＋dp/dtmax）和左心室内压下降最大速率（-dp/dtmax）显著低于正常组,左室舒张末压（LVEDP）显著高于正常组（P〈0.05）,血脂康组各指标明显改善,与正常组比较无显著统计学差异。模型组SERCA2a表达显著低于正常组（P〈0.05）,而血脂康组SERCA2a表达明显升高,较正常组无显著差异。结论：血脂康可以改善链脲佐菌素致糖尿病大鼠心功能不全,与其对SERCA2a的改善作用相关。     

血脂康对自发性高血压大鼠心肌重构的作用及其可能机制

目的观察血脂康(Xuezhikang,XZK)对自发性高血压大鼠(spontaneously hypertensive rats,SHR)左室肥厚和心肌间质纤维化的影响,探究其可能机制。方法 30只SHR,♂,随机分为3组,血脂康(300 mg.kg 1.d 1)治疗组(XZK组,n=10),辛伐他汀(5 mg.kg 1.d 1)治疗组(SIM组,n=10),SHR对照组(SHR组,n=10),同时入组同龄Wistar-Kyoto大鼠为正常对照组(WKY组,n=10),均予等容量0.9%生理盐水灌胃。12周后,分离心脏,左室称重并计算左室重量指数(LVWI),心肌组织固定包埋后Masson染色并计算心肌胶原容积分数(CVF)及心肌血管周围胶原面积(PVCA),测定血清Ⅰ型前胶原羧基末端前肽(PⅠCP)浓度、心肌组织超氧歧化酶(SOD)活性及丙二醛(MDA)浓度。结果与SHR组相比,XZK组和SIM组可以显著降低LVWI(P<0.05)、CVF(P<0.01)、PVCA(P<0.01)及血清PⅠCP浓度(P<0.01),但SOD活力及MDA浓度差异无统计学意义。结论血脂康能够显著减轻SHR的左室肥厚,降低心肌间质纤维化程度,并与血压和胆固醇水平的变化无关,血脂康表现出与辛伐他汀相同的抗心肌重构作用,作用机制可能与心肌SOD活性和MDA浓度相关不大。