芪参益气滴丸辅助治疗冠心病伴心力衰竭的疗效及对患者心功能指标、血液流变学和血清NT-proBNP、Hcy水平的影响.pdf

海南医学2023年8月第34卷第15期Hainan Med J,Aug.2023,Vol.34,No.15芪参益气滴丸辅助治疗冠心病伴心力衰竭的疗效及对患者心功能指标、血液流变学和血清NT-proBNP、Hcy水平的影响常建1，平英瑶1，苏志祥21.榆林市中医医院心血管内科，陕西榆林719000；2.神木市医院中医科，陕西榆林719300【摘要】目的探究芪参益气滴丸辅助治疗冠心病(CHD)伴心力衰竭的疗效及对患者心功能指标、血液流变学和血清N-末端脑钠肽前体(NT-proBNP)、同型半胱氨酸(Hcy)水平的影响。方法选取2019年3月至2022年5月榆林市中医医院收治的84例CHD伴心力衰竭患者作为研究对象，采用随机数表法分为观察组和对照组各42例，对照组患者给予常规抗心衰治疗，观察组患者给予常规治疗联合芪参益气滴丸辅助治疗，两组均治疗2周，比较两组患者的治疗效果，以及治疗前后的心功能指标、血液流变学指标和血清NT-proBNP、Hcy水平。结果观察组患者的治疗总有效率为95.24%，明显高于对照组的80.95%，差异有统计学意义(P0.05)；治疗后，两组患者的心室射血分数(LVEF)、每分钟排血量(CO)均升高，且观察组患者的LVEF、CO分别为(47.605.50)%、(5.300.30)L/min，明显高于对照组的(43.504.40)%、(4.900.40)L/min，差异均有统计学意义(P0.05)；治疗后，两组患者的左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)均降低，且观察组患者的LVEDD、LVESD分别为(53.202.50)mm、(39.103.7)mm，明显低于对照组的(57.103.40)mm、(42.604.10)mm，差异均有统计学意义(P0.05)；治疗后，两组患者的血液流变学指标均降低，且观察组患者的血浆黏度、红细胞压积、全血黏度高切、全血黏度低切水平明显低于对照组，差异均有统计学意义(P0.05)；治疗后，两组患者的血清 NT-proBNP、Hcy 水平均降低，且观察组患者的NT-proBNP、Hcy分别为(1 367.2491.55)pg/mL、(14.314.55)mol/L，明显低于对照组的(1 864.5196.37)pg/mL、(17.374.82)mol/L，差异均有统计学意义(P0.05)。结论芪参益气滴丸辅助常规治疗CHD伴心力衰竭可改善患者的心功能及血液流变学指标，降低血清NT-proBNP、Hcy水平，从而提高治疗效果，具有临床应用价值。【关键词】冠心病；心力衰竭；芪参益气滴丸；心功能；血液流变学【中图分类号】R541.4【文献标识码】A【文章编号】10036350（2023）15215005Efficacy of Qishen Yiqi Dripping Pills as adjuvant treatment for coronary heart disease with heart failure and theinfluence on cardiac function indicators,hemorheology,serum NT-proBNP,and Hcy levels.CHANG Jian1,PINGYing-yao1,SU Zhi-xiang2.1.Department of Cardiovascular Medicine,Yulin Traditional Chinese Medicine Hospital,Yulin719000,Shaanxi,CHINA;2.Department of Traditional Chinese Medicine,Shenmu Hospital,Yulin 719300,Shaanxi,CHINA【Abstract】ObjectiveTo investigate the efficacy of Qishen Yiqi Dripping Pills as adjuvant treatment for coro-nary heart disease(CHD)with heart failure,and its influence on cardiac function indicators,hemorheology,serum N-ter-minal pro-brain natriuretic peptide(NT-proBNP),and homocysteine(Hcy)levels.MethodsA total of 84 patients withCHD and heart failure who were admitted to Yulin Traditional Chinese Medicine Hospital from March 2019 to May2022 were selected as the study subjects.They were divided into the control group(treated with conventional anti-heartfailure therapy)and the observation group(treated with anti-heart failure therapy combined with Qishen Yiqi DrippingPills)by random number table method,with 42 cases in each group.All patients underwent 2 weeks of treatment.Thetwo groups were compared in terms of therapeutic effect,cardiac function indicators,hemorheological indicators,serumNT-proBNP,and Hcy levels before and after treatment.ResultsThe total treatment response rate in the observationgroup was significantly higher than that in the control group(95.24%vs 80.95%,P0.05).After treatment,left ventricu-lar ejection fraction(LVEF)and cardiac output(CO)in the two groups increased;LVEF and CO in the observationgroup were(47.605.50)%and(5.300.30)L/min,significantly higher than(43.504.40)%and(4.900.40)L/min inthe control group;the differences were statistically significant(P0.05).After treatment,left ventricular end-diastolic di-ameter(LVEDD)and left ventricular end-systolic diameter(LVESD)in the two groups decreased;LVEDD and LVESDin the observation group were(53.202.50)mm and(39.103.70)mm,significantly smaller than(57.103.40)mm and(42.604.10)mm in the control group;the differences were statistically significant(P0.05).After treatment,hemorheo-logical indicators in the two groups decreased;plasma viscosity,hematocrit,whole blood high-shear viscosity,andlow-shear viscosity in the observation group were significantly lower than those in the control group;the differenceswere statistically significant(P0.05)，具有可比性，见表1。本研究经我院医学伦理委员会审核批准。the levels of NT-proBNP and Hcy in the observation group were(1 367.2491.55)pg/mL and(14.314.55)mol/L,sig-nificantly lower than(1 864.5196.37)pg/mL and(17.374.82)mol/L in the control group;the differences were statisti-cally significant(P0.05).ConclusionQishen Yiqi Dripping Pills as adjuvant treatment for conventional treatment canimprove cardiac function and hemorheological indicators,and lower serum NT-proBNP and Hcy levels in patients withCHD and heart failure,thereby improving the therapeutic effect.【Key words】Coronary heart disease;Heart failure;Qishen Yiqi Dripping Pills;Cardiac function;Hemorheology表1两组患者的一般资料比较 x-s，例(%)Table 1Comparison of general information between the two groups x-s,n(%)组别对照组观察组2/t/Z值P值例数4242男20(47.62)18(42.86)女22(52.38)24(57.14)0.1920.661年龄(岁)57.436.1558.766.080.9970.322级23(54.76)22(52.38)级17(40.48)19(45.24)级2(4.76)1(2.38)心力衰竭病程(年)2.420.462.590.331.9460.055心功能0.0110.915性别1.2治疗方法对照组患者采用常规抗心衰治疗。根据 中国心力衰竭诊断和治疗指南20186常规应用抗心力衰竭、抗凝治疗，采用血管紧张素转换酶抑制剂、非甾体抗炎药等进行治疗。观察组患者在对照组治疗的基础上联合芪参益气滴丸辅助治疗，芪参益气滴丸(天士力制药集团股份有限公司，Z20030139，0.5 g15袋)饭后半小时口服，使用频率与时间为0.5 g/次，3次/d。两组疗程均为2周。1.3观察指标与评价(检测)方法(1)疗效7：治疗2周后比较两组患者的治疗效果。显效：全身乏力、呼吸困难等临床症状消失，心功能改善2级(或达级)；有效：症状减轻且心功能改善1级(未达级)；未达上述标准即无效。有效率=(显效数+有效数)/例数100%。(2)心功能指标：采用超声心动图测量两组患者治疗前后的左心室射血分数(left ventricular ejectionfraction，LVEF)、左心室舒张/收缩末期内径(left ven-tricular end diastolic/systolic diameter，LVEDD/LVESD)及每分钟排血量(cardiac output，CO)。(3)血液流变学指标：采用LG-R-80A血液流变仪检测两组患者治疗前后的血浆黏度、红细胞压积、全血黏度高切、全血黏度低切水平。(4)血清NT-proBNP、Hcy水平：于治疗前后抽取两组患者肘中静脉血3 mL，分别采用双向测流免疫法及酶联免疫分析法测定NT-proBNP、Hcy水平。1.4统计学方法应用 SPSS20.0统计软件分析2151海南医学2023年8月第34卷第15期Hainan Med J,Aug.2023,Vol.34,No.15数据。计量资料符合正态分布，以均数标准差(x-s)表示，组间与组内比较分别采用独立样本t检验与配对样本t检验；计数资料比较采用2检验，等级资料比较采用秩和检验。以P0.05为差异有统计学意义。2结果2.1两组患者的治疗效果比较观察组患者的治疗总有效率为95.24%，明显高于对照组的80.95%，差异有统计学意义(2=4.086，P=0.0430.05)；治疗后，两组患者的LVEF、LVEDD、LVESD、CO均得到改善，且观察组患者的LVEF、CO明显高于对照组，LVEDD、LVESD明显低于对照组，差异均有统计学意义(P0.05)；治疗后，两组患者的血浆黏度、红细胞压积、全血黏度高切/低切水平均降低，且观察组明显低于对照组，差异均有统计学意义(P0.05)；治疗后，两组患者的血清NT-proBNP、Hcy水平均降低，且观察组明显低于对照组，差异均有统计学意义(P0.05)，见表5。表2两组患者的治疗效果比较(例)Table 2Comparison of therapeutic effects between the two groups(n)组别对照组观察组例数4242显效1922有效1518无效82总有效率(%)80.9595.24表3 两组患者治疗前后的心功能指标比较(x-s)Table 3Comparison of cardiac function indicators between the two groups before and after treatment(x-s)组别对照组观察组t值P值例数4242治疗前39.804.3040.104.100.3270.744治疗后43.504.40a47.605.50a3.7720.001治疗前61.104.1060.804.200.3310.741治疗后57.103.40a53.202.50a5.9890.001治疗前46.305.0046.504.800.1870.852治疗后42.604.10a39.103.70a4.1070.001治疗前4.600.604.400.501.6600.101治疗后4.900.40a5.300.30a5.1850.001注：与本组治疗前比较，aP0.05。Note:Compared with that in the same group before treatment,aP0.05.LVEF(%)LVEDD(mm)LVESD(mm)CO(L/min)表4 两组患者治疗前后的血液流变学指标比较(x-s)Table 4Comparison of hemorheological indicators between the two groups before and after treatment(x-s)组别对照组观察组t值P值例数4242治疗前1.400.031.390.051.1110.270治疗后1.260.11a1.200.16a2.0030.049治疗前47.805.1048.104.800.2780.782治疗后45.105.60a41.206.00a3.0800.003治疗前5.460.555.590.571.0640.291治疗后5.120.43a4.930.38a2.1460.035治疗前14.151.8614.061.910.2190.827治疗后13.052.06a11.401.97a3.7520.001血浆黏度(mPa s)红细胞压积(%)全血黏度高切(mPa s)全血黏度低切(mPa s)注：与本组治疗前比较，aP0.05。Note:Compared with that in the same group before treatment,aP0.05.3讨论心力衰竭为各种严重心脏疾病终末阶段的临床综合征，病情复杂，预后效果欠佳，病死率与致残率高。西医在治疗心力衰竭方面虽具有一定优势，但仍存在药物费用昂贵、疗效欠佳等不足之处。现阶段中西医结合为我国治疗心力衰竭的临床基本模式之一8，中医认为，心力衰竭属本虚标实之症，本虚以气虚为主，标实则以血瘀为主，气虚无法推动血行，久病入络则致血瘀9。芪参益气滴丸为纯中药制剂，具有活血益气等功效，为提升治疗及预后效果，本研究采用芪参益气滴丸辅助治疗CHD伴心力衰竭。本研究结果显示，观察组患者的治疗有效率明显高于对照组。究其原因：黄芪、丹参、降香、三七为芪参益气滴丸的主要有效成分，其中黄芪归于肺、肝、肾、脾经，具有敛汗固脱、益气固表之效；丹参可止痛祛瘀、活血调经；降香与三七则具有活血止痛、活血祛瘀之效，多方合用共奏祛瘀行滞、活血益气之效10，辅助西药治疗后效果更显著。治疗后两组患者的心功能指表5两组患者治疗前后的血清NT-proBNP、Hcy水平比较(x-s)Table 5Comparison of serum NT-proBNP and Hcy levels betweenthe two groups before and after treatment(x-s)组别对照组观察组t值P值例数4242治疗前2 456.43156.382 503.75161.301.3650.176治疗后1 864.5196.37a1 367.2491.55a24.2450.001治疗前24.055.1623.875.080.1610.872治疗后17.374.82a14.314.55a2.9920.004NT-proBNP(pg/mL)Hcy(mol/L)注：与本组治疗前比较，aP0.05。Note:Compared with that in the same group before treatment,aP0.05.2152Hainan Med J,Aug.2023,Vol.34,No.15海南医学2023年8月第34卷第15期标均得到改善，且观察组改善更显著，提示芪参益气滴丸辅助治疗可显著改善患者心功能指标。心力衰竭的发生发展机制为神经内分泌激活与心室重塑，芪参益气滴丸方中的黄芪可调节蛋白激酶 C(proteinkinase C，PKC)的活性，抑制炎症因子释放，保护冠状动脉血管内皮功能11，抑制LVEDD扩大，进而达到改善整体左室功能的效果。血液循环障碍可导致血浆渗透压上升，此时细胞处脱水状态(细胞黏度增加)进而发生血液流变学改变12。CHD患者存在血液循环障碍导致脂肪及肌肉组织长期处于缺氧状态，进而释放大量的氨基酸与脂肪酸刺激肝脏合成大量纤维蛋白原13，导致机体凝血功能亢进，血浆黏度升高，因此血流速度改变。治疗后两组患者的血浆黏度、红细胞压积等水平均降低，且观察组明显低于对照组，提示采用芪参益气滴丸辅助治疗可改善CHD伴心力衰竭患者血液流变学指标。相关研究表明血清NT-proBNP、Hcy水平可反映CHD心力衰竭的发展状态，NT-proBNP在心肌细胞压力负荷升高与受到容量负荷时由左心室分泌，为诊断心力衰竭的特异性标志物14-15。Hcy可致血管内皮细胞损伤、影响低密度脂蛋白(low densitylipoprotein，LDL)的氧化并在多因素作用下导致心脏功能减退，Hcy水平越高表明心脑血管疾病的危险性越高。两组治疗后血清NT-proBNP、Hcy水平均降低，观察组低于对照组，提示采用芪参益气滴丸辅助治疗可降低患者血清NT-proBNP、Hcy水平，究其原因：现代药理学研究表明芪参益气滴丸中的黄芪具有降低外周阻力、减少心脏负荷等作用同时可对心肌细胞超微结构进行保护，丹参则可改善缺血心肌的能量代谢，通过改善心肌功能以达到降低血清NT-proBNP、Hcy水平的作用。张凯旋等16同样采用芪参益气滴丸辅助常规治疗对CHD伴心力衰竭患者进行干预，结果显示患者心功能得到改善且血清NT-proBNP水平降低，本研究与其结果相似，进一步表明芪参益气滴丸在治疗CHD伴心力衰竭方面具有良好的应用价值。综上所述，采用芪参益气滴丸辅助治疗CHD伴心力衰竭可显著提升疗效，改善患者心功能及血液流变学指标并降低血清 NT-proBNP、Hcy水平，具有临床应用价值。参考文献1Henning RJ.Diagnosis and treatment of heart failure with preservedleft ventricular ejection fraction J.World J Cardiol,2020,12(1):7-25.2Zhao ZY,Jin J,Yu R.Effect of 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Medicine,2021,38(7):863-867.张凯旋,耿巍,田祥,等.常规治疗联合芪参益气滴丸治疗冠心病慢性心力衰竭的疗效观察J.天津中医药,2021,38(7):863-867.(收稿日期：2022-12-07)曲妥珠单抗联合化疗方案治疗乳腺癌的疗效及其作用机制研究陆佳团，王征，张浩南阳市中心医院乳腺科一病区，河南南阳473200【摘要】目的评价曲妥珠单抗联合化疗方案治疗乳腺癌(BC)的疗效，并探讨其对患者外周血磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)通路的干预作用。方法选取2019年3月至2021年1月南阳市中心医院乳腺科一病区收治的68例BC患者为研究对象，采用奇偶分组法分为单一组和联合组各34例。单一组患者予以TP方案(紫杉醇+顺铂)化疗，联合组患者予以曲妥珠单抗+TP方案化疗，两组连续治疗3个周期。比较两组患者的临床疗效及治疗前后的血清肿瘤标志物癌胚抗原(CEA)、糖类抗原125(CA125)、糖类抗原153(CA153)、生化指标血小板第4因子(PF4)、中期因子(MK)、脂质运载蛋白-2(LCN-2)水平；比较两组患者治疗前后的外周血PI3K/Akt通路相关蛋白磷酸化磷脂酰肌醇-3-激酶(p-PI3K)、磷酸化蛋白激酶B(p-AKT)表达量、生活质量欧洲癌症研究与治疗组织生命质量测定量表(EORTC QLQ-C30)及毒副反应发生率。随访1年后，比较两组患者的生存率。结果联合组患者的治疗总有效率、疾病控制率分别为44.12%、79.41%，明显高于单一组的20.59%、47.06%，差异均有统计学意义(P0.05)；治疗后，联合组患者的血清CEA、CA125、CA153、PF4、MK、LCN-2水平和p-PI3K、p-AKT蛋白表达量明显低于单一组，差异均有统计学意义(P0.05)；治疗后，联合组患者的EORTC QLQ-C30评分为(116.329.13)分，明显高于单一组的(101.248.46)分，差异有统计学意义(P0.05)；联合组患者的总生存率为93.75%，明显高于单一组的72.41%，差异有统计学意义(P0.05)。结论曲妥珠单抗联合TP化疗方案可提高BC患者的临床疗效，降低肿瘤标志物和生化指标水平，提高生存率，且具有一定安全性，其可能通过抑制PI3K/Akt通路活化发挥作用。【关键词】乳腺癌；曲妥珠单抗；化疗；PI3K/Akt通路；疗效【中图分类号】R737.9【文献标识码】A【文章编号】10036350（2023）15215405Efficacy and mechanism of Trastuzumab combined with chemotherapy in the treatment of breast cancer.LUJia-tuan,WANG Zheng,ZHANG Hao.Ward,Breast Department,Nanyang Central Hospital,Nanyang 473200,Henan,CHINA【Abstract】ObjectiveTo evaluate the efficacy of Trastuzumab combined with chemotherapy in the treatmentof breast cancer(BC),and to explore its intervention effect on the phosphatidylinositol-3-kinase(PI3K)/protein kinaseB(Akt)pathway in peripheral blood.MethodsSixty-eight BC patients admitted to Ward,Breast Department,Nan-yang Central Hospital from March 2019 to January 2021 were selected as the research subjects.The patients were divid-ed into a single group(n=34)and a combined group(n=34)using parity grouping method.The single group received TP 论著 doi:10.3969/j.issn.100