目的 探讨葛根芩连汤（GGQLD）对KK-Ay糖尿病小鼠血浆中脂多糖（LPS）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）的量及肠道菌群的调节作用。方法 以普通饲料喂养的C57BL/6J小鼠作为对照组，ig等量蒸馏水。将高脂饲料喂养的KK-Ay小鼠分为5组，吡格列酮组和模型组分别ig给予盐酸吡格列酮5 mg/kg和等量蒸馏水，GGQLD高、中、低剂量组ig分别给予GGQLD生药40、13.3、4.44 g/kg。各组均连续给药4周后，以鲎试剂显色基质法测定血浆中LPS的量，用酶联免疫吸附试验法（ELISA）检测血浆中TNF-α及IL-6的水平，采用变性梯度凝胶电泳（DGGE）技术分析小鼠肠道菌群的结构。结果 与模型组相比，GGQLD高、中剂量组均能显著降低小鼠血浆内LPS的量（P< 0.05），分别降低了15.61%、14.48%；GGQLD高、中、低剂量组IL-6的量与模型组比较分别下降了56.86%、37.12%、30.21%，具有一定的剂量依赖性，且有统计学意义（P< 0.05）；GGQLD高、中、低剂量组TNF-α的量均明显低于模型组（P< 0.05），分别下降了28.32%、30.70%、23.42%。GGQLD高剂量组DGGE图谱条带数目明显增多，且经克隆、测序和Blast比对分析，约翰逊氏乳杆菌Lactobacillus johnsonii为GGQLD高剂量组特有，说明GGQLD可明显调节肠道菌群结构。结论 GGQLD抗2型糖尿病胰岛素抵抗作用可能与其改善LPS、TNF-α、IL-6等炎症因子，及调节肠道菌群结构相关。

Objective To explore the effect of Gegen Qinlian Decoction (GGQLD) on LPS, TNF-α, IL-6, and intestinal flora in diabetic KK-Ay mice. Methods C57BL/6J mice with ordinary feed were taken as the normal control group and orally administrated with equal distilled water. The KK-Ay mice fed with high-fat diet were divided into five groups: pioglitazone group, blank group (model group), high, medium, and low dose GGQLD group, and orally administrated with pioglitazone hydrochloride (5 mg/kg), distilled water, and GGQLD (crude drug 40, 13.3, and 4.44 g/kg), respectively. The oral administration for six groups lasted for four weeks. Tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and endotoxin (LPS) levels in the plasma were determined by enzyme-linked immunosorbent assay (ELISA); Gut microbial communities were assayed by polymerase chain reaction (PCR) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) methods. Results Compared with the model group, the LPS levels in the plasma of mice were significantly reduced by 15.61% and 14.48% respectively in the Gegenqinlian Decoction of high and medium dose group (P < 0.05), the IL-6 levels in plasma of mice were significantly reduced by 56.86%, 37.12% and 30.21% respectively in high, medium, and low dose GGQLD group (P < 0.05), and the TNF-α levels in plasma of mice were significantly reduced by 28.32%, 30.70%, and 23.42% respectively in high, medium, and low dose GGQLD group (P < 0.05). The number of DGGE bands in high dose group significantly increased, and by cloning, sequencing, and Blast analysis, Lactobacillus johnsonii only existed in the high dose group; The results showed that GGQLD could regulate the structure of intestinal flora in KK-Ay mice. Conclusion The mechanisms of anti-diabetic effects of GGQLD in type 2 diabetic KK-Ay mice are probably related with the anti-inflammation and regulation of intestinal flora.

国家自然科学基金资助项目（81460622，81260660）；江西省自然科学基金资助项目（20151BAB205079，20151BAB205077）；江西省卫生计生委科研计划项目（2016A024）