黄芪多糖联合顺铂治疗卵巢癌相关恶性腹水的疗效及对耐药基因的影响

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目的:探讨黄芪多糖联合顺铂治疗卵巢癌相关恶性腹水的疗效及对耐药基因的影响。方法:选择2015年1月至2018年12月山东省广饶县中医院诊治的卵巢癌相关恶性腹水患者120例,根据患者住院号奇、偶数分成顺铂治疗组和黄芪多糖联合顺铂治疗组,每组60例,顺铂治疗组给予顺铂75 mg/mn 2,加入0.9%氯化钠50 ml稀释后从腹腔引流管推入,灌注后夹闭引流管,每3 d灌注1次,连续治疗21 d,共灌注治疗7次;黄芪多糖联合顺铂治疗组在顺铂治疗组的基础上联合注射用黄芪多糖250 ml静脉滴注,1次/d,治疗21 d。两组治疗结束后从腹腔引流管抽吸腹水行后续检测。比较两组不良反应、腹水复发时间和中位生存期的差异。检测并比较两组患者治疗前后炎性因子和T淋巴细胞改变。采用逆转录聚合酶链反应(RT-PCR)和Western blot检测两组治疗后腹水耐药基因谷胱甘肽S-转移酶π(GST-π)、P-糖蛋白(P-gp)和多药耐药基因1(MDR1)mRNA和蛋白质表达,并进行比较。n 结果:黄芪多糖联合顺铂治疗组患者治疗后消化道症状、Ⅲ~Ⅳ级骨髓抑制、Ⅲ~Ⅳ级肝肾功能损伤发生率均低于顺铂治疗组[38.3%(23/60)比66.7%(40/60)、6.7%(4/60)比33.3%(20/60)、13.3%(8/60)比45.0%(27/60)],腹水复发时间及中位生存期高于顺铂治疗组[(6.3 ± 1.7)个月比(5.5 ± 1.1)个月、(15.2 ± 2.4)个月比(11.7 ± 1.6)个月],差异均有统计学意义(n P0.05),治疗后黄芪多糖联合顺铂治疗组TNF-α和IL-6低于顺铂治疗组[(21.8 ± 3.5)ng/L比(27.5 ± 4.1)ng/L,(17.2 ± 2.2)ng/L比(21.9 ± 2.7)ng/L],IL-2高于顺铂治疗组[(15.5 ± 1.6)ng/L比(12.7 ± 1.1)ng/L],差异有统计学意义(n P0.05),治疗后黄芪多糖联合顺铂治疗组CDn 3+、CDn 4+和CDn 8+水平高于顺铂治疗组[(55.3 ± 3.9)%比(48.9 ± 3.2)%、(33.2 ± 3.4)%比(30.4 ± 2.2)%、(21.4 ± 3.1)%比(17.6 ± 1.9)%],差异有统计学意义(n P<0.05)。黄芪多糖联合顺铂治疗组治疗后腹水GST-π、P-gp和MDR1基因mRNA和蛋白质表达均显著低于顺铂治疗组,差异有统计学意义(n P<0.05)。n 结论:黄芪多糖可改善卵巢癌相关恶性腹水患者免疫功能,降低耐药基因表达,显著提高顺铂治疗卵巢癌相关恶性腹水的疗效,并降低不良反应。“,”Objective:To study the efficacy of astragalus polysaccharides combined with cisplatin in the treatment of malignant peritoneal effusion caused by ovarian cancer and its effect on drug resistance genes.Methods:Patients with malignant peritoneal effusion caused by ovarian cancer from January 2015 to December 2018 in Guangrao Country Hospital of Traditional Chinese Medicine were selected as the study subjects. They were divided into astragalus polysaccharide combined with cisplatin treatment group and cisplatin treatment group according to the odd and even number of hospital number, with 60 patients in each group. The patients in cisplatin treatment group were given peritoneal perfusion with cisplatin 75 mg/mn 2 and 0.9% sodium chloride injection 50 ml, and the drainage tube were clamped once every 3 d. Treatment continued for 21 d. The patients in astragalus polysaccharide combined with cisplatin treatment group were treated with astragalus polysaccharide 250 ml intravenous drip once a day on the basis of cisplatin treatment group, and treatment continued for 21 d. The peritoneal effusion was pumped by drainage tube and was detected after treatment. The differences in adverse reactions, ascites recurrence time and median survival time were compared between two groups. Changes in inflammatory factors and T lymphocytes before and after treatment were detected and compared. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect resistance genes in peritoneal effusions including glutathione S-transferase π (GST-π), P-glycoprotein (P-gp) and multidrug resistance gene 1 (MDR1) mRNA and protein expression.n Results:The incidence of gastrointestinal symptoms, Ⅲ-Ⅳ class myelosuppression and Ⅲ-Ⅳ class hepatorenal damage in the astragalus polysaccharide combined with cisplatin treatment group were significantly lower than those in the cisplatin treatment group [38.3%(23/60) vs. 66.7%(40/60), 6.7%(4/60) vs. 33.3%(20/60), 13.3%(8/60) vs. 45.0%(27/60)], while the ascites recurrence time and median survival time were significantly higher than those in the cisplatin treatment group [(6.3 ± 1.7) months vs. (5.5 ± 1.1) months, (15.2 ± 2.4) months vs. (11.7 ± 1.6) months], and there were significant differences (n P0.05), after treatment in astragalus polysaccharide combined with cisplatin treatment group, the levels of TNF-α and IL-6 were lower [(21.8 ± 3.5) ng/L vs. (27.5 ± 4.1) ng/L, (17.2 ± 2.2) ng/L vs. (21.9 ± 2.7) ng/L] and the level of IL-2 was higher [(15.5 ± 1.6)ng/L vs. (12.7 ± 1.1) ng/L], and there were significant differences (n P0.05), after treatment in astragalus polysaccharide combined with cisplatin treatment group, the levels of CDn 3+, CDn 4+ and CDn 8+ were higher [(55.3 ± 3.9)% vs. (48.9 ± 3.2)%, (33.2 ± 3.4)% vs. (30.4 ± 2.2)%, (21.4 ± 3.1)% vs. (17.6 ± 1.9)%], and there were significant differences (n P<0.05). After treatment, the levels of GST-π, P-gp and MDR1 gene mRNA and protein expressions in astragalus polysaccharide combined with cisplatin treatment group were significantly lower than those in the cisplatin treatment group, and there were significant differences (n P<0.05).n Conclusions:Astragalus polysaccharide can improve immune function and reduce drug resistance gene expression in patients with malignant peritoneal effusion caused by ovarian cancer, which can significantly improve the efficacy of cisplatin in the treatment of malignant peritoneal effusion caused by ovarian cancer and reduce adverse reactions.
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