气血瘀滞型非小细胞肺癌患者“瘀毒”病机临床特征及补肺化瘀汤辅助治疗干预机制

Clinical Characteristics of Stasis-Toxin Pathogenesis in Patients with NonsmallCell Lung Cancer of Blood Stasis and Qi Stagnation Syndrome and theInterventional Mechanism of Adjuvant Therapy with Bufei Huayu Decoction

【目的】探讨气血瘀滞型非小细胞肺癌(non-small cell lung cancer,NSCLC)患者“瘀毒”病机的临床特征以及补肺化瘀汤辅助治疗的干预机制。【方法】选取六安市中医院呼吸内科2021年1月至2022年9月收治的78例气血瘀滞型NSCLC患者作为NSCLC组,另选取71例同期健康体检志愿者为健康对照组,观察NSCLC组“瘀毒”病机的临床特征,比较2组凝血功能指标的差异。根据治疗方式的不同将NSCLC组患者分为补肺化瘀组40例和常规治疗组38例,常规治疗组采用常规化疗方案治疗,补肺化瘀组在常规治疗组的基础上加用补肺化瘀汤治疗,以3周为1个疗程,共治疗2个疗程。观察2组患者治疗前后中医证候积分、生活质量Karnofsky功能状态(KPS)评分、凝血功能、免疫功能、血清一氧化氮(NO)、血管内皮生长因子(VEGF)水平的变化情况,比较2组患者的临床疗效和治疗期间不良反应发生情况。【结果】(1)临床特征方面,NSCLC组患者临床分期为Ⅲ、Ⅳ期,病理类型为鳞癌、腺癌,KPS评分低于70分患者比例较高,中医证候积分较高,提示NSCLC患者病情较为严重;与健康对照组相比,NSCLC组患者的凝血酶原时间(PT)、凝血酶时间(TT)明显缩短,纤维蛋白原(FIB)、D-二聚体(D-D)水平明显升高,差异均有统计学意义(P<0.01)。(2)疗效方面,治疗6周后,补肺化瘀组的总有效率和总稳定率分别为32.50%(13/40)、85.00%(34/40),明显优于常规治疗组的13.16%(5/38)、60.53%(23/38),差异均有统计学意义(P<0.05)。(3)证候积分方面,治疗3周后,补肺化瘀组的各项中医证候积分(包括神疲乏力、胸闷气短、胸部刺痛、脉络瘀血等)和常规治疗组的神疲乏力、胸闷气短积分均较治疗前改善(P<0.05);治疗6周后,2组NSCLC患者的各项中医证候积分均较治疗前和治疗3周后改善(P<0.05);组间比较,除治疗3周后的胸闷气短外,补肺化瘀组在治疗3周和6周后对各项中医证候积分的改善作用均明显优于常规治疗组(P<0.05或P<0.01)。(4)凝血功能方面,治疗6周后,补肺化瘀组的PT、TT、FIB、D-D水平均较治疗前明显改善(P<0.05),而常规治疗组仅FIB、D-D水平较治疗前改善(P<0.05);组间比较,补肺化瘀组对PT、FIB、D-D水平的改善作用均明显优于常规治疗组(P<0.05)。(5)血清NO、VEGF水平方面,治疗6周后,2组患者的血清NO、VEGF水平均较治疗前明显降低(P<0.05),且补肺化瘀组的降低作用均明显优于常规治疗组(P<0.01)。(6)免疫功能方面,治疗6周后,补肺化瘀组的T细胞亚群CD3^(+)、CD4^(+)水平和CD4^(+)/CD8^(+)比值较治疗前升高(P<0.05)、CD8^(+)水平较治疗前降低(P<0.05),而常规治疗组的CD3^(+)、CD4^(+)水平及CD4^(+)/CD8^(+)比值较治疗前降低(P<0.05)、CD8^(+)水平较治疗前升高(P<0.05);组间比较,补肺化瘀组对CD3^(+)、CD4^(+)水平和CD4^(+)/CD8^(+)比值的升高作用及对CD8^(+)水平的降低作用均明显优于常规治疗组(P<0.01)。(7)生活质量方面,治疗6周后,2组患者的KPS评分均较治疗前明显升高(P<0.05),且补肺化瘀组的升高作用明显优于常规治疗组(P<0.01)。(8)不良反应方面,治疗过程中,2组患者的胃肠道反应、脱发的发生率比较,差异无统计学意义(P>0.05),而补肺化瘀组的肝肾功能损伤、骨髓抑制、口腔黏膜毒性的不良反应发生率均明显低于常规治疗组(P<0.05或P<0.01),表明补肺化瘀汤可一定程度上降低化疗所引起的不良反应。【结论】气血瘀滞型NSCLC患者普遍病情进展程度深,血液凝滞性高,契合中医“瘀毒”病机;针对“瘀毒”病机使用补肺化瘀汤治疗可明显改善患者中医证候积分和凝血功能,下调血清NO、VEGF水平,改善患者免疫功能,可提高患者临床疗效及生活质量,减少化疗所带来的不良反应,具有较高的安全性。

Objective To investigate the clinical characteristics of stasis-toxin pathogenesis in patients with nonsmall cell lung cancer(NSCLC)of blood stasis and qi stagnation type,and to explore the interventional mechanism of adjuvant therapy with Bufei Huayu Decoction.Methods Seventy-eight patients with NSCLC of blood stasis and qi stagnation type admitted to the Department of Respiratory Medicine of Liu’an Hospital of Traditional Chinese Medicine from January 2021 to September 2022 were selected as the NSCLC group,and 71 volunteers who underwent physical examination during the same period served as the healthy control group.The clinical characteristics of stasis-toxin pathogenesis in the NSCLC group were observed,and the differences in the indicators of coagulation function were compared between NSCLC group and the healthy control group.According to the therapy,the NSCLC patients were divided into Bufei Huayu Decoction group(40 cases)and conventional treatment group(38 cases).The conventional treatment group was treated with conventional chemotherapy,while Bufei Huayu Decoction group was treated with Bufei Huayu Decoction together with conventional chemotherapy.Three weeks constituted one course of treatment,and the treatment lasted for 2 courses.The changes of traditional Chinese medicine(TCM)syndrome scores,Karnofsky Performance Status(KPS)score,coagulation function,immune function,serum nitric oxide(NO),vascular endothelial growth factor(VEGF)level in Bufei Huayu Decoction group and conventional treatment group were observed before and after treatment.Moreover,the clinical efficacy of the two groups and the occurrence of adverse reactions were compared during the treatment period.Results(1)NSCLC patients were classified into the clinical stagesⅢandⅣand the pathological types of squamous carcinoma and adenocarcinoma,had the high proportion of KPS scores lower than 70,and were scored with high TCM syndrome scores,suggesting that the illness condition of patients with NSCLC was serious.Compared with the healthy control group,plasminogen time(PT)and thrombin time(TT)in NSCLC patients were significantly shortened,and levels of fibrinogen(FIB)and D-dimer(D-D)were significantly increased,and the differences were statistically significant(P<0.01).(2)After 6 weeks of treatment,the total effective rate and total stability rate of Bufei Huayu Decoction group were 32.50%(13/40)and 85.00%(34/40),which were significantly superior to those of the conventional treatment group[versus 13.16%(5/38)and 60.53%(23/38)],and the differences were statistically significant(P<0.05).(3)After 3 weeks of treatment,obvious improvement was presented in the scores of all the TCM symptoms of fatigue,chest distress and shortness of breath,stabbing pain in the chest,and blood stasis in the vessels and collaterals of Bufei Huayu Decoction group and in the scores of the fatigue,chest distress and shortness of breath of the conventional treatment group when compared with those before treatment(P<0.05).After 6 weeks of treatment,all of the TCM syndrome scores of the two groups were improved compared with those before treatment and after three weeks of treatment(P<0.05).The intergroup comparison showed that except for the scores of chest distress and shortness of breath after 3 weeks of treatment,the effect on improving all of the TCM syndrome scores in Bufei Huayu Decoction group was significantly superior to that in the conventional treatment group after 3 and 6 weeks of treatment(P<0.05 or P<0.01).(4)After 6 weeks of treatment,the levels of coagulation function indicators of PT,TT,FIB and D-D in the Bufei Huayu Decoction group were significantly improved compared with those before treatment(P<0.05),while only FIB and D-D in the conventional treatment group were improved compared with those before treatment(P<0.05).The intergroup comparison showed that Bufei Huayu Decoction group had stronger effect on improving the levels of PT,FIB and D-D than the conventional treatment group(P<0.05).(5)After 6 weeks of treatment,the serum NO and VEGF levels in both groups were significantly lower than those before treatment(P<0.05),and the effect on lowering serum NO and VEGF levels of the Bufei Huayu Decoction group was significantly superior to that of the conventional treatment group(P<0.01).(6)After 6 weeks of treatment,the immune function parameters of CD3^(+),CD4^(+)levels and CD4^(+)/CD8^(+)ratio in the Bufei Huayu Decoction group were increased(P<0.05)and CD8^(+) level was decreased(P<0.05)as compared with those before treatment,whereas CD3^(+),CD4^(+) levels and CD4^(+)/CD8^(+) ratio in the conventional treatment group were decreased(P<0.05)and CD8^(+) level was increased(P<0.05). The intergroup comparison showed that the effect of Bufei Huayu Decoction group on the increase of CD3^(+),CD4^(+) levels and CD4^(+)/CD8^(+) ratio and the effect on the decrease of CD8^(+) level were significantly superior to those ofthe conventional treatment group(P<0.01).(7)In terms of the quality of life,the KPS scores of patients in thetwo groups after 6 weeks of treatment were significantly higher than those before treatment(P<0.05),and theeffect of Bufei Huayu Decoction group on the increase of KPS scores was significantly superior to that of theconventional treatment group(P<0.01).(8)During the course of treatment,the incidence of adverse reactionssuch as gastrointestinal reactions and alopecia in the two groups was not statistically significant(P>0.05),whilethe incidence of hepatic and renal impairment,bone marrow suppression,and toxicity of oral mucosa in BufeiHuayu Decoction group was significantly lower than that of the conventional treatment group(P<0.05 or P<0.01),suggesting that Bufei Huayu Decoction group reduced the adverse reactions induced by chemotherapy to acertain extent. Conclusion Patients with NSCLC of blood stasis and qi stagnation type generally have advanceddisease progression and high blood coagulation,which is consistent with the stasis-toxin pathogenesis in TCM. Theuse of Bufei Huayu Decoction against the stasis- toxin pathogenesis can significantly improve patients’TCMsyndrome scores and coagulation function,down-regulate the levels of serum NO and VEGF,and improve theimmune function,which brings about the enhancement of clinical efficacy and quality of life,and the reduction ofadverse reactions caused by chemotherapy,with a high safety.