目的 探討注射用益氣復脈（凍干）（YQFM）對阿霉素導致的心肌損傷大鼠的藥效作用及對腸道菌群的影響。方法 將24只阿霉素導致心肌損傷模型成功的SD大鼠隨機分為3組：模型組和YQFM低、高劑量（464.3、928.6 mg·kg^-1）組，另取8只健康SD大鼠為對照組。每天尾iv給藥1次，連續(xù)14 d，對照組和模型組尾iv 0.9%氯化鈉注射液。給藥過程中觀察大鼠狀態(tài)并稱體質(zhì)量。給藥結(jié)束后，酶聯(lián)免疫吸附（ELISA）法檢測大鼠血清中超氧化物歧化酶（SOD）、丙二醛（MDA）、乳酸脫氫酶（LDH）和肌酸激酶（CK）水平；取出心臟進行HE染色觀察病理改變；取出盲腸位置糞便，進行高通量16S rRNA測序分析。結(jié)果 對照組大鼠一般狀態(tài)正常，模型組出現(xiàn)毛色變差、厭食、腹脹、腹瀉、口鼻出血、眼球出血的動物數(shù)明顯多于給藥組；與對照組比較，模型組大鼠體質(zhì)量顯著降低（P<0.001）；與模型組比較，YQFM低、高劑量組的大鼠體質(zhì)量顯著上升（P<0.01、0.001）。與對照組相比，模型組MDA、LDH、CK水平均顯著升高，SOD活性顯著性下降（P<0.001） ；與模型組比較，YQFM低、高劑量組MDA、LDH、CK水平顯著下降，SOD活性顯著升高（P<0.001）。HE結(jié)果顯示，對照組心肌細胞排列整齊，模型組有心肌細胞溶解和出血現(xiàn)象，給予YQFM后心肌細胞溶解和出血現(xiàn)象減輕。Alpha多樣性分析結(jié)果顯示，與對照組相比，模型組腸道菌群的多樣性和豐度均顯著下降（P<0.05、0.01） ；與模型組比較，YQFM組腸道菌群的多樣性和豐度顯著上升（P<0.05、0.01、0.001）。距離矩陣與PCoA分析結(jié)果顯示，給藥組和對照組之間的差異比模型組和對照組的差異小。腸道豐度的結(jié)果顯示，與對照組相比，模型組在門和屬的水平上的菌群數(shù)量均顯著減少（P<0.01） ；與模型組比較，YQFM低劑量組在門的水平上和低、高劑量組在屬的水平上菌群數(shù)量均顯著增加（P<0.01、0.001）。在菌群物種的組成差異度分析中，與模型組比較，給予YQFM后有助于有益菌的生長和抑制致病菌生長（P<0.05、0.01、0.001） ；在腸道菌群均勻度的分析中，與對照組比，模型組的腸道菌群均勻度降低，給予YQFM后，腸道菌群的均勻度恢復。結(jié)論 YQFM對阿霉素導致的大鼠心肌損傷發(fā)揮改善作用，并且可改善心肌損傷造成的腸道菌群多樣性及豐度下降，抑制致病菌的生長，促進有益菌的生長。

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.

R285.5