TAN Yan,ZHOU Cong,HUANG Rou,et al.Effect of Yinchenhao Tang on Type 2 Diabetes Mellitus Complicated with Non-alcoholic Fatty Liver Disease in MKR Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(21):105-113.
TAN Yan,ZHOU Cong,HUANG Rou,et al.Effect of Yinchenhao Tang on Type 2 Diabetes Mellitus Complicated with Non-alcoholic Fatty Liver Disease in MKR Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(21):105-113. DOI: 10.13422/j.cnki.syfjx.20212195.
Effect of Yinchenhao Tang on Type 2 Diabetes Mellitus Complicated with Non-alcoholic Fatty Liver Disease in MKR Mice
To investigate the action mechanism of Yinchenhao Tang against type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) in MKR mice.
Method
2
Forty eight-week-old MKR mice were fed a high-fat diet for eight weeks and then divided into the model group,original Yinchenhao Tang (17.16 g·kg
-1
) group,Yinchenhao Tang group at a specified dose (4.68 g·kg
-1
) in teaching materials,and positive drug [metformin + simvastatin, (65+2.6)×10
-3
g·kg
-1
] group. Another 10 MKR mice of the same age were classified into the blank group and 10 FVB mice into the normal group. After eight weeks of intragastric administration in each group,the liver wet weight,oral glucose tolerance test (OGTT),serum inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-
α
(TNF-
α
),and changes in blood lipid and liver function were determined. Hematoxylin-eosin (HE) staining was conducted for observing the morphological changes in liver tissue under a transmission electron microscope,followed by the detection of Toll-like receptor 4 (TLR4),myeloid differentiation factor 88 (MyD88),and nuclear transcription factor-
κ
B (NF-
κ
B) protein expression by Western blot.
Result
2
Compared with the model group,the medication groups exhibited significantly reduced liver wet weight index (
P
<
0.01),improved OGTT result (
P
<
0.05),and down-regulated serum IL-6 and TNF-
α
levels (
P
<
0.01). In terms of morphological changes,Yinchenhao Tang protected the hepatocyte structure and alleviated hepatocyte steatosis. Moreover, Yinchenhao Tang obviously down-regulated the protein expression levels of TLR4,MyD88,and NF-
κ
B in liver tissue of MKR mice with T2DM combined with NAFLD (
P
<
0.05),and the down-regulation of TLR4 and NF-
κ
B in the original Yinchenhao Tang group was better than that in the Yinchenhao Tang group at a specified dose in teaching materials (
P
<
0.05).
Conclusion
2
Yinchenhao Tang is able to reduce inflammatory factor levels and down-regulate TLR4,MyD88,and NF-
κ
B expression in liver tissue to relieve the pathological liver injury and interfere with T2DM combined with NAFLD of MKR mice. It exerts a certain liver-protective effect by lowering the blood lipids and delaying the hepatic inflammation.
关键词
Keywords
references
BRIL F , CUSI K . Management of nonalcoholic fatty liver disease in patients with type 2 diabetes:a call to action [J]. Diabetes Care , 2017 , 40 ( 3 ): 419 - 430 .
XU L , XIE T , SHEN T , et al . Yinchenhaotang for chronic hepatitis B:protocol for a systematic review and Meta-analysis [J]. Medicine , 2019 , 98 ( 8 ): e14648 .
XUE M , DERVISH S , HARRISON L C , et al . Activated protein C inhibits pancreatic islet inflammation,stimulates T regulatory cells,and prevents diabetes in non-obese diabetic(NOD) mice [J]. J Biol Chem , 2012 , 287 ( 20 ): 16356 - 16364 .
HAZLEHURST J M , WOODS C , MARJOT T , et al . Non-alcoholic fatty liver disease and diabetes [J]. Metabolism , 2016 , 65 ( 8 ): 1096 - 1108 .
SCHUSTER S , CABRERA D , ARRESE M , et al . Triggering and resolution of inflammation in NASH [J]. Nat Rev Gastroenterol Hepatol , 2018 , 15 ( 6 ): 349 - 364 .
YAN F J , WANG X , WANG S E , et al . C-Jun/C7ORF41/NF- κ B axis mediates hepatic inflammation and lipid accumulation in NAFLD [J]. Biochem J , 2020 , 477 ( 3 ): 691 - 708 .