引经药桔梗在养阴药物治疗干燥综合征中发挥“引药上行”的作用研究

Study on the role of Platycodon grandiflorum in the treatment of Sjogren’s syndrome

目的 研究引经药桔梗能否形成对增液汤治疗干燥综合征的增效减毒作用,并初步探索相应的机制。方法 将自发型干燥综合征模型NOD小鼠随机分为模型组、增液汤、增桔组,另选取ICR小鼠作为对照组。对照组和模型组给予生理盐水灌胃,其他组给予相应的药物治疗。药物治疗7周。灌胃期间检测小鼠的唾液流率,灌胃结束后处死小鼠,取出颌下腺进行病理评价,免疫组化法测定颌下腺AQP5和VIP的表达,流式检测颈部淋巴结CD8^(+)T细胞的比例、采用三代测序检测小鼠肠道微生态的变化。结果 与对照组比较,模型组16周龄时小鼠的唾液流率明显下降(P=0.0027),颌下腺中VIP和AQP5的表达均下降(P<0.0001,P=0.0013),颌下腺病理评分和颈部淋巴结中CD8^(+)T细胞比例均升高,肠道微生态提示模型组肠道微生态a多样性指数均较对照组有降低趋势。与模型组比较,增液汤组和增桔组小鼠VIP和AQP5的表达以及小鼠唾液流率均升高,颌下腺病理评分和颈部淋巴结中CD8^(+)T细胞比例均降低,增液汤对肠道微生态的丰度改善无明显作用,但增桔组可明显改善肠道微生态a多样性Shannon和Pielou指数;与增液汤组相比,增桔组小鼠唾液流率以及VIP和AQP5的表达均进一步升高。结论 桔梗可以增强增液汤对干燥综合征治疗的作用,促进津液向上分布,且能改善肠道微生态,具有“引药上行”的作用。

Objective To study whether Platycodon grandiflorum can form a synergistic and attenuated effect on Zengye Decoction in the treatment of Sjogren 's syndrome, and to explore the corresponding mechanism. Methods NOD mice with spontaneous Sjogren 's syndrome were randomly divided into model group, Zengye Decoction group and Zengjie group, and ICR mice were selected as control group. The control group and the model group were given normal saline by gavage, and the other groups were given corresponding drug treatment. Drug treatment for 7 weeks. The salivary flow rate of the mice was detected during the gavage. After the gavage, the mice were sacrificed and the submandibular glands were removed for pathological evaluation. The expression of AQP5 and VIP in the submandibular glands was determined by immunohistochemistry. The proportion of CD8^(+) T cells in cervical lymph nodes was detected by flow cytometry. The changes of intestinal microecology in mice were detected by third-generation sequencing. Results Compared with the control group, the salivary flow rate of mice in the model group decreased significantly at 16 weeks of age(P= 0.0027), the expression of VIP and AQP5 in submandibular gland decreased(P< 0.0001,P= 0.0013), the pathological score of submandibular gland and the proportion of CD8^(+) T cells in cervical lymph nodes increased, and the intestinal microecology suggested that the intestinal microecology a diversity index of the model group was lower than that of the control group. Compared with the model group, the expression of VIP and AQP5 and the salivary flow rate of mice in the Zengye Decoction group and the Zengjie group were increased, the pathological score of submandibular gland and the proportion of CD8^(+) T cells in cervical lymph nodes were decreased. Zengye Decoction had no significant effect on the abundance of intestinal microecology, but Zengjie group could significantly improve the intestinal microecology a diversity Shannon and Pielou index;compared with the Zengye decoction group, the salivary flow rate and the expression of VIP and AQP5 in the Zengjie group were further increased. Conclusion Platycodon grandiflorum can enhance the effect of Zengye Decoction on the treatment of Sjogren 's syndrome, promote the upward distribution of body fluid, and improve the intestinal microecology, which has the effect of “carrying body fluid upward”.