Effect of Dendrobium officinale Polysaccharides in Reversing Hepatic Fibrosis in Rats via Notch Signaling Pathway and Ultrasound Evaluation
10.13422/j.cnki.syfjx.20241206
- VernacularTitle:铁皮石斛多糖基于Notch信号通路抗大鼠肝纤维化作用及其超声评价
- Author:
Ying XU
1
;
Jina LUO
1
;
Liuqing YANG
2
;
Qianqian TIAN
1
;
Jiamao CHENG
2
;
Haiyan CHEN
1
Author Information
1. School of Clinical Medicine，Dali University，Dali 671003，China
2. School of Basic Medical Sciences，Dali University，Dali 671003，China
- Publication Type:Journal Article
- Keywords:
Dendrobium officinale polysaccharides;
hepatic fibrosis;
Notch signaling pathway;
ultrasound evaluation;
Young's modulus
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(21):70-77
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect of Dendrobium officinale polysaccharides （DOP） in reversing carbon tetrachloride （CCl4）-induced hepatic fibrosis （HF） in rats via the Notch signaling pathway and evaluate the therapeutic effect of DOP by ultrasound elastography. MethodFifty-six male SD rats were randomized into normal， model， colchicine （1×10-4 g·kg-1）， Fuzheng Huayu powder （0.45 g·kg-1）， and low-， medium-， and high-dose （0.05， 0.1， 0.2 g·kg-1） DOP groups （n=8）. The rats in the model group and each treatment group were injected subcutaneously with a mixture of CCl4-olive oil （2∶3） once every 3 days for 10 weeks. After 6 weeks of modelling， the rats were administrated with corresponding drugs once a day for 4 weeks. Hematoxylin-eosin （HE） staining and Masson staining were employed to observe the pathomorphological changes of the liver tissue. An automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， and total bile acids （TBA）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the serum levels of hyaluronic acid （HA）， laminin （LN）， type Ⅲ precollagen （PC-Ⅲ）， and type Ⅳ collagen （Col-Ⅳ）. The mRNA and protein levels of α-smooth muscle actin （α-SMA）， Notch1， Jagged1， and Hes1 in the liver tissue were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The Young's modulus （YM） of the rat liver was measured by acoustic radiation force impulse （ARFI） elastography before and after treatment. Then， the correlations of YM with the serum levels of HA， LN， PC-Ⅲ， and Col-Ⅳ and the protein levels of α-SMA and Notch1 signaling pathway-related factors in the liver tissue were analyzed. ResultCompared with the normal group， the model group showed disordered arrangement of liver cell cords， obvious infiltration of inflammatory cells， appearance of a large number of fat vacuoles， and fibrous proliferation， elevated levels of ALT， AST， TBA， ALP， HA， LN， PC-Ⅲ， and Col-Ⅳ in the serum， and up-regulated mRNA and protein levels of α-SMA， Notch1， Jagged1， and Hes1 in the liver tissue （P<0.01）. Compared with the model group， drug interventions alleviated the pseudolobule formation and the collagen deposition in confluent areas. Except that the serum level of ALT in the low-dose DOP group had no significant changes， drug interventions， especially high-dose DOP， lowered the levels of ALT， AST， TBA， ALP， HA， LN， PC-Ⅲ， and Col-Ⅳ in the serum and down-regulated the mRNA and protein levels of α-SMA， Notch1， Jagged1， and Hes1 in the liver tissue （P<0.05， P<0.01）. The results of ARFI and correlation analysis showed that the YM of the liver tissue was increased in the model group （P<0.01） compared with that in the normal group， Compared with the model group， drug interventions decreased YM （P<0.01）. YM was positively correlated with the expression levels of HA， LN， PC-Ⅲ， α-SMA， Notch1， Jagged1， and Hes1s （r=0.754， 0.734， 0.801， 0.885， 0.896， 0.757， and 0.800， respectively， P<0.01）， and it had a moderate correlation with Col-Ⅳ （r=0.688， P<0.01）. ConclusionDOP can reverse HF by down-regulating the Notch1/Jagged1/Hes1 signaling pathway. YM can be used as an indicator in the assessment of the efficacy of DOP against HF.
