[Effect of Compound Zhajin Granule on Toll-like Receptor 4 Signaling Pathway in Nonalcoholic Steatohepatitis Mice].
OBJECTIVE
To observe the effect of Compound Zhajin Granule (CZG) on Toll-like re-ceptor 4 (TLR4) signaling pathway in high-fructose corn syrup induced NASH mice.


METHODS
Thirty 6-week-old male C3H mice were divided into the high fat and high fructose (HFHFr) group (n = 20) and the control group (n = 10) according to body weight. Mice in the HFHFr group ate high fat diet and drank 20% fructose water, while those in the control group ate common diet and drank common water. After 8 weeks mice in the HFHFr group were divided into two group according to body weight, the HFHFr group and the CZG group, 10 in each group. Mice in the CZG group were fed with high fat forage and 20% fructose water, and administered with 50 mL/kg 12. 8% CZG (prepared by hawthorn, Radix Curcumae, Alisma Orientale, Fritillaria Thunbergii, Silybum Marianum, peach seed in the ratio of 3:1.5:1.5:2:1.5:2:1) by gastrogavage. Mice in the HFHFr group were fed in the same way and daily administered with equal volume of distilled water by gastrogavage. Sixteen weeks later all mice were sacrificed. Body weight, liver wet weight, liver function, and lipid metabolism were detected. Pathological changes of liver tissues were assessed by HE staining, oil red O staining, and Masson staining. Expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor-alpha (TNF-α) were detected using immunohistochemical staining and real-time fluorescent quantitative PCR.


RESULTS
Body weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST) were obviously lower in the CZG group than in the HFHFr group (P < 0.05); oil red O stained area and density were decreased more in the CZG group than in the control group. HE staining showed ballooning inflammation was reduced more in the CZG group than in the HFHFr group. Masson staining was negative. Positive rates of TLR4 and MyD88 and mRNA expressions were significantly lower in the CZG group than in the HFHFr group (all P < 0.05).


CONCLUSIONS
CZG could significantly inhibit TLR4 signaling pathway of liver in NASH mice.
Jing
J
Liu
Zhen-jie
ZJ
Zhuang
Jing
J
Tian
Zhao-yi
ZY
Li
Yan
Y
Luo
Yin-lan
YL
Liu
Jian-yu
JY
Chen
Xiao-jie
XJ
Ma
Shu-fei
SF
Zang
Jun-ping
JP
Shi
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D059305:Diet, High-Fat; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects; D007249:Inflammation; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004365:Drugs, Chinese Herbal; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D005632:Fructose; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase