1.北京中医药大学东直门医院 北京 100700
2.北京中医药大学中医学院
穆国华,男,在读博士生
# 通信作者:赵进喜,博士,教授,主任医师,博士生导师,主要研究方向:中医药对肾病内分泌疾病防治,E-mail:zhaojinximd@126.com
收稿:2020-08-30,
纸质出版:2021-02-28
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穆国华, 赵宗江, 周婧雅, 等. 黄连肉桂对db/db小鼠肠道菌群、炎性因子及短链脂肪酸的影响[J]. 北京中医药大学学报, 2021,44(2):134-142.
Guohua Mu, Zongjiang Zhao, Jingya Zhou, et al. Effects of
穆国华, 赵宗江, 周婧雅, 等. 黄连肉桂对db/db小鼠肠道菌群、炎性因子及短链脂肪酸的影响[J]. 北京中医药大学学报, 2021,44(2):134-142. DOI: 10.3969/j.issn.1006-2157.2021.02.008.
Guohua Mu, Zongjiang Zhao, Jingya Zhou, et al. Effects of
目的
2
研究黄连肉桂对db/db小鼠的降糖作用,探讨其对db/db小鼠肠道菌群、炎症因子及短链脂肪酸(SCFAs)的影响机制。
方法
2
以6只db/m小鼠为空白组,30只db/db小鼠随机分成5组,模型组给予等量的生理盐水,其他4组分别用二甲双胍(0.23 g/kg)、黄连(18.20 g/kg)、肉桂(1.82 g/kg)及黄连肉桂进行干预。0、8周测量各组小鼠的体重,在0、4、8周分别测量各组小鼠的血糖,第8周时采集各组小鼠粪便,利用Illumina Miseq平台测序,进行门群菌落物种分析、多样性分析;气相色谱法检测粪便中乙酸、丙酸、正丁酸含量;利用Western blot方法检测小鼠肝脏肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)表达。
结果
2
黄连肉桂组小鼠体重增长趋势减缓,高血糖状态改善,与模型组相比差异有统计学意义(
P
<
0.05);与空白组相比,模型组及二甲双胍组小鼠厚壁菌门(Firmicutes)丰度增加,拟杆菌门(Bacteroides)丰度下降。与模型组及二甲双胍组相比,中药3组的厚壁菌门(Firmicutes)丰度下降,黄连、肉桂组拟杆菌门(Bacteroides)丰度增加;肉桂组、黄连肉桂组放线菌门(Actinobacteria)的丰度增加。空白组与模型组之间物种菌群组成丰度差异明显,二甲双胍组与模型组物种组成丰度相似,黄连组、肉桂组与空白组丰度接近,黄连肉桂组与其余组物种组成丰度均存在差异;abundance曲线示中药3组小鼠肠道菌群丰度及均匀度较其他各组降低,提示黄连肉桂可能通过抑制某些菌落的生长,从而使得肠道内形成新的菌群结构。模型组小鼠肝脏TNF-α含量较空白组明显增多(
P
<
0.05)。黄连肉桂组TNF-α含量较模型组明显降低(
P
<
0.05);与空白组比较,模型组小鼠肝脏IL-6含量明显增多(
P
<
0.05),黄连组、肉桂组、黄连肉桂组IL-6较模型组明显降低(
P
<
0.05,
P
<
0.01)。黄连肉桂组提高SCFAs中乙酸、丙酸、丁酸的含量,与模型组比差异有统计学意义(
P
<
0.05),各干预组中黄连肉桂组更具优势,其均值高于其他干预组。
结论
2
黄连肉桂可能通过调节db/db小鼠肠道菌群、改善小鼠炎症反应及增加SCFAs含量达到对2型糖尿病的防治作用。
Objective
2
To study the hypoglycemic effect of
Huanglian
(coptis
Rhizoma Coptidis
) and
Rougui
(cinnamon bark
Cortex Cinnamomi
) on db/db mice
and to explore the mechanism of its effect on the intestinal flora
inflammatory factors and short-chain fatty acids (SCFAs) in db/db mice.
Methods
2
Six db/m mice were included in the blank group
and 30 db/db mice were randomly divided into the model group
metformin group
coptis group
cinnamon bark group and coptis and cinnamon bark group (
n
=6). In the four treatment groups
metformin (0.23g/kg)
coptis (18.2g/kg)
cinnamon bark (1.82g/kg) and coptis and cinnamon bark were gavaged with the corresponding drugs respectively
and the control group was gavaged with the same amount of normal saline solution. The body weight of each group of mice was measured at week 0 and 8
and the blood glucose was measured at week 0
4
and 8. The feces of each group of mice were taken at the 8th week for analysis of phylum flora species and species diversity analysis with Illunina MiSeq benchtop sequencer. The content of acetic acid
propionic acid
and n-butyric acid in feces were detected by gas chromatography. The expression of TNF-α and IL-6 in the liver of mice was detected by Western blot.
Results
2
The weight gain trend of the mice slowed down and the hyperglycemia state improved in the coptis and cinnamon group
compared with the model group (
P
<
0.01). The abundance of Firmicutes was increased
while that of the Bacteroidetes was decreased in the control group and three treatment groups with Chinese medicinals
compared with the blank group. The abundance of Firmicutes was decreased in the three treatment groups with Chinese medicinals
while the abundance of the Bacteroidetes was increased in the coptis group and cinnamon bark group
compared with the control group and metformin group. Regarding species diversity
there was significant difference between the blank group and control group
similarity between the control group and metformin group
similarity among the coptis group
cinnamon bark group
and blank group
while differences between the coptis and cinnamon bark group and any other group. The abundance curve showed that the abundance and uniformity of the intestinal flora of the three treatment groups were lower than those of the other groups. The content of TNFα in the liver of mice in the control group was significantly higher than that in the blank group (
P
<
0.05)
but it was significantly lower in the coptis and cinnamon bark group than that of the control group (
P
<
0.05). The content of IL-6 in the liver of mice in the control group was significantly increased compared with the blank group (
P
<
0.05)
but it was significantly lower in all the three treatment groups with Chinese medicinals compared with that of the control group (
P
<
0.05
P
<
0.01). The contents of acetic acid
propionic acid and butyric acid in SCFAs were significantly increased in the coptis and cinnamon bark group
compared with the control group (
P
<
0.05). The coptis and cinnamon bark group showed a higher mean score compared with the other three treatment groups.
Conclusion
2
Huanglian
(coptis
Rhizoma Coptidis
) and
Rougui
(cinnamon bark
Cortex Cinnamomi
) may help in the prevention and treatment of type 2 diabetes by regulating the intestinal flora
improving the inflammatory response
and increasing the content of SCFAs.
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