探讨半夏泻心汤联合盐酸伊立替康治疗对大鼠肠道菌群的影响

目的 探讨半夏泻心汤对盐酸伊立替康（irinotecan hydrochloride，CPT-11）相关的大鼠肠道菌群的影响。方法 选取70只雄性大鼠适应性喂养1周后，采用随机数字表法分为空白对照组、模型对照组、半夏泻心汤低剂量组、半夏泻心汤中剂量组、半夏泻心汤高剂量组、5-氨基水杨酸组，以及半夏泻心汤+5-氨基水杨酸组，每组10只。所有大鼠腹腔注射CPT-11溶液造模，根据组别和剂量分别对各组灌胃半夏泻心汤和5-氨基水杨酸。10d后麻醉处死大鼠取材，测量大鼠胃残留率、小肠推进率。采用16S rDNA测序分析大鼠肠道粪便中的菌群种类，采用香浓–威纳（Shannon-wiener）指数计算各组大鼠粪便样品中菌群的多样性。采用索雷森（Sorenson）指数比较各组大鼠肠道菌群16S rDNA-PCR-DGGE图谱的相似性。结果 相比于空白对照组，模型组大鼠增重缓慢，胃残留率升高，肠推进率降低，菌群多样性指数和相似性指数降低，肠杆菌数量增多，拟杆菌、双歧杆菌、肠球菌和乳酸杆菌数量减少，差异均有统计学意义（P<0.05）；与模型对照组相比，半夏泻心汤低、中、高剂量组大鼠的胃残留率降低，肠推进率提高，肠杆菌数量减少，拟杆菌、双歧杆菌、肠球菌和乳酸杆菌数量增多，差异均有统计学意义（P<0.05）；与半夏泻心汤中剂量组比较，半夏泻心汤与5-氨基水杨酸联合治疗后，大鼠的肠推进率提高，拟杆菌、双歧杆菌、肠球菌和乳酸杆菌增多，差异均有统计学意义（P<0.05）。治疗后第10天，半夏泻心汤各剂量组、5-氨基水杨酸组、半夏泻心汤+5-氨基水杨酸组的菌群多样性指数、菌群相似性指数均显著高于模型对照组（P<0.05），且半夏泻心汤中剂量组的菌群多样性指数、菌群相似性指数显著高于半夏泻心汤低、高剂量组（P<0.05）；半夏泻心汤+5-氨基水杨酸组的菌群多样性指数、菌群相似性指数均显著高于5-氨基水杨酸组（P<0.05），结论 半夏泻心汤能够显著改善大鼠由CPT-11导致的肠道菌群失调现象，缓解大鼠体质量下降的症状，使得模型大鼠胃残留率降低、肠推进率增加。

To investigate the effect of Banxia Xiexin decoction combined with irinotecan on intestinal flora of experimental rats

Objective To explore the effect of Banxia Xiexin decoction on intestinal flora of rats related to irinotecan hydrochloride (CPT-11). Method Seventy male rats were selected and fed for 1 week after acclimatization, and were divided into blank control group, model control group, low dose group of Banxia Xiexin decoction, medium dose group of Banxia Xiexin decoction, high dose group of Banxia Xiexin decoction, 5-aminosalicylic acid group, and Banxia Xiexin decoction + 5-aminosalicylic acid group according to the random number table method, with 10 rats in each group. All rats were injected intraperitoneally with CPT-11 solution, and each group was given gavage of Banxia Xiexin decoction and 5-aminosalicylic acid according to the group and dose. 10 days later, the rats were anesthetized and executed for sampling, and the gastric residual rate and small intestinal advancement rate were measured. The 16S rDNA sequencing was used to analyze the species of flora in rat intestinal feces, and Shannon-wiener index was used to calculate the diversity of flora in each group of rat fecal samples. The similarity of 16S rDNA-PCR-DGGE profiles of rat intestinal flora in each group was compared using Sorenson index. Results Compared with the blank control group, the rats in the model control group gained more weight slowly, had higher gastric residual rate, increased the number of enterobacter, decreased the number of bacteroide, bifidobacterium, enterococcus and lactobacillus, all with statistically significant differences (P<0.05). Compared with the model control group, the rats in the low, medium and high dose groups of Banxia Xiexin decoction showed lower gastric residual rate, higher intestinal advancement rate, lower numbers of enterobacteriaceae and higher numbers of bacteroide, bifidobacterium, enterococcus and lactobacillus, all with statistically significant differences (P<0.05). Compared with the medium dose group of Banxia Xiexin decoction, the combination treatment of Banxia Xiexin decoction and 5-aminosalicylic acid resulted in increased intestinal propulsion rate, and increased the numbers of bacteroide, bifidobacterium, enterococcus and lactobacillus in rats, all with statistically significant differences (P<0.05). On the 10th day after treatment, the flora diversity index and flora similarity index of each dose group, the 5-aminosalicylic acid group and the group of Banxia Xiexin decoction + 5-aminosalicylic acid were significantly higher than those of the model control group (P<0.05), and the flora diversity index and flora similarity index of the middle dose group of Banxia Xiexin decoction were significantly higher than those of the low and high dose groups of Banxia Xiexin decoction (P<0.05). The diversity index and similarity index of bacterial flora in the group ofBanxia Xiexin decoction + 5-aminosalicylic acid were significantly higher than those in the group of 5-aminosalicylic acid (P<0.05). Conclusion Banxia Xiexin decoction can significantly improve the intestinal microflora disorder caused by CPT-11 in rats, alleviate the symptoms of weight loss in rats, and reduce the gastric residual rate and increase the intestinal thrust rate of model rats.