[关键词]
[摘要]
目的 探讨注射用益气复脉(冻干)(YQFM)对阿霉素导致的心肌损伤大鼠的药效作用及对肠道菌群的影响。方法 将24只阿霉素导致心肌损伤模型成功的SD大鼠随机分为3组:模型组和YQFM低、高剂量(464.3、928.6 mg·kg-1)组,另取8只健康SD大鼠为对照组。每天尾iv给药1次,连续14 d,对照组和模型组尾iv 0.9%氯化钠注射液。给药过程中观察大鼠状态并称体质量。给药结束后,酶联免疫吸附(ELISA)法检测大鼠血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、乳酸脱氢酶(LDH)和肌酸激酶(CK)水平;取出心脏进行HE染色观察病理改变;取出盲肠位置粪便,进行高通量16S rRNA测序分析。结果 对照组大鼠一般状态正常,模型组出现毛色变差、厌食、腹胀、腹泻、口鼻出血、眼球出血的动物数明显多于给药组;与对照组比较,模型组大鼠体质量显著降低(P<0.001);与模型组比较,YQFM低、高剂量组的大鼠体质量显著上升(P<0.01、0.001)。与对照组相比,模型组MDA、LDH、CK水平均显著升高,SOD活性显著性下降(P<0.001) ;与模型组比较,YQFM低、高剂量组MDA、LDH、CK水平显著下降,SOD活性显著升高(P<0.001)。HE结果显示,对照组心肌细胞排列整齐,模型组有心肌细胞溶解和出血现象,给予YQFM后心肌细胞溶解和出血现象减轻。Alpha多样性分析结果显示,与对照组相比,模型组肠道菌群的多样性和丰度均显著下降(P<0.05、0.01) ;与模型组比较,YQFM组肠道菌群的多样性和丰度显著上升(P<0.05、0.01、0.001)。距离矩阵与PCoA分析结果显示,给药组和对照组之间的差异比模型组和对照组的差异小。肠道丰度的结果显示,与对照组相比,模型组在门和属的水平上的菌群数量均显著减少(P<0.01) ;与模型组比较,YQFM低剂量组在门的水平上和低、高剂量组在属的水平上菌群数量均显著增加(P<0.01、0.001)。在菌群物种的组成差异度分析中,与模型组比较,给予YQFM后有助于有益菌的生长和抑制致病菌生长(P<0.05、0.01、0.001) ;在肠道菌群均匀度的分析中,与对照组比,模型组的肠道菌群均匀度降低,给予YQFM后,肠道菌群的均匀度恢复。结论 YQFM对阿霉素导致的大鼠心肌损伤发挥改善作用,并且可改善心肌损伤造成的肠道菌群多样性及丰度下降,抑制致病菌的生长,促进有益菌的生长。
[Key word]
[Abstract]
Objective To investigate the pharmacodynamic and intestinal flora effect of Yiqi Fumai Lyophilized Injection (YQFM) on adriamycin induced myocardial injury in rats. Methods Totally 24 SD rats with myocardial injury induced by adriamycin were randomly divided into three groups:model group, YQFM low and high-dose group (464.3 and 928.6 mg·kg-1). Another eight healthy SD rats were taken as control group. Tail vein iv 0.9% sodium chloride injection was administered in control and model group, and tail vein iv YQFM was used in the administration group continuously for 14 days. During the administration process, the rats were observed and weighed. After the administration, the contents of superoxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH) and creatine kinase (CK) in the serum of rats were detected by enzyme-linked immunosorbent assay (ELISA). The heart was taken out for HE staining to observe the pathological changes. Feces from the cecum were removed and analyzed by high-throughput 16Sr RNA sequencing. Results The rats in the control group were in normal state, while the number of animals in the model group with hair color deterioration, anorexia, abdominal distension, diarrhea, oral and nasal bleeding, and eyeball bleeding were significantly more than those in the administration group. Compared with control group, the body weight of the model group was significantly decreased (P<0.001). Compared with model group, the body weight of rats in YQFM low and high dose groups was significantly increased (P<0.001). Compared with control group, the contents of MDA, LDH and CK in model group were significantly increased and the activity of SOD was significantly decreased (P<0.001). After administration, the contents of MDA, LDH and CK in YQFM group decreased, while the activity of SOD increased (P<0.001). HE stain results showed that the cardiomyocytes in control group were arranged in order, and cardiomyocytes in model group were dissolved and bleeding, which were alleviated after YQFM adminintration. The results of alpha diversity analysis showed that compared with control group, the diversity and abundance of intestinal flora in model group decreased (P<0.05 and 0.01), while compared with model group, after YQFM adminintration, the diversity and abundance of intestinal flora increased and recovered(P<0.05 and 0.01). The results of distance matrix and PCoA analysis showed that the difference between the YQFM administration group and the control group was smaller than that between the model group and the control group (P<0.01). The results of intestinal abundance showed that compared with control group, the number of phylum and genus in model group decreased (P<0.01), and compared with model group, the number of bacteria in the low dose YQFM group at the phylum level and the low and high dose YQFM groups at the genus level were significantly increased (P<0.01, 0.001). In the analysis of the composition difference of the flora species, YQFM was helpful to the growth of beneficial bacteria and inhibit the growth of pathogenic bacteria compared with model group (P<0.01, 0.001). In the analysis of evenness of intestinal flora, compared with control group, the evenness of intestinal flora in model group decreased, and after YQFM adminintration, the evenness of intestinal flora recovered. Conclusion YQFM can improve the myocardial injury caused by doxorubicin in rats, and improve the diversity and abundance of intestinal microbiota caused by myocardial injury, inhibit the growth of pathogenic bacteria, and promote the growth of beneficial bacteria.
[中图分类号]
R285.5
[基金项目]