Protective Effects Of BSC On Liver Fibrosis Induced By Bile Duct Ligation

Hepatic fibrosis，a kind of liver injuries which result from the inflammation triggeredby the long-term chronic irritation of various pathogenic factors，will lead to the excessivedeposition of ECM in the process of tissue repair。Hepatic fibrosis is the early and reversiblephase of the liver cirrhosis，which will develop into the liver cirrhosis even cancer，if there isno timely treatment.。It can be seen that hepatic fibrosis has been a huge threat to human’ shealth。Therefore，it is really meaningful to search for a kind of effective and anti-fibrosismedicine。BSC，a new drug deliverer, is the combination of the berinine and sodium caprate。It isreally helpful to solve many problems，such as the low bioavailability caused by the lowwater solubility of berinine and the poor permeability of intestinal mucosa。It is reported andconfirmed that berinine has the pharmacologic effects to protect the liver and to be againstfibrosis。Because of its low bioavailability，in order to achieve the pharmacologic effects thedose of drug has to be increased，which will lead to huge toxic and side effects。Therefore，studying the liver protection and mechanism of BSC is of great significance in thedevelopment of liver-protective medicine。Studies have shown that oxidative stress is closely related to hepatic fibrosis。First ofall，lipid peroxidation caused by oxidative stress can promote the activation，proliferationand collagen synthesis，which accelerate hepatic fibrosis。Besides，ROS of the oxidativestress will promote the activation of protein kinase B，which can accelerate the combinationof translation initiation complex，as a result, the collagen synthesis will be increased。Next，in oxidative stress，ROS can promote the secretion of transforming growth factor-β1(TGF-β1)by adjusting KLF6[2]，TGF-β1can mediate the differentiation of HSC and thegeneration of collagen，and it can activate NADPH oxidase (NXO)，which is the main sourceof ROX。As the mark of the activation of HSC，α-smooth muscle actin(α-SMA) has alsoincreased in hepatic fibrosis。 Therefore，BOS、NOX、TGF-β1、AKT and α-SMA all playthe important role in the occurrence and development of hepatic fibrosis，the restraint on the generation and activation may prove to be the significant point in the protection of liver。It isfound in the study that AMP-activated protein kinase (AMPK)，as a kind of energy sensingenzyme，exists widely in the eukaryotic cells to adjust the energy metabolism of theorganism。The latest researches have found that AMPK can also suppress the activation ofNOX，which can diminish the generation of ROS，that is to say, the activation of AMPK canbe used as a mechanism to protect the liver or suppress the development of the hepaticfibrosis。Objects：The research studied the protective effect of solid dispersion on hepaticfibrosis and discussed on the correlation between its anti-fibrosis effect and TGF-β1、NOX4、AKT、α-SMA and. AMPK。Methods：The bile duct ligation (BDL) was used in the study to induce the hepaticfibrosis model of the rats，which were divided into Group Sham、Group Hepatic FibrosisModel、Group High Dose (solid dispersion50mg/kg)、Group Low Dose (solid dispersion25mg/kg)、and Group Silybin Positive Comparison。The rats were killed after five weeks totest alanine transarninase (ALT)、glutamic-oxal(o)acetic transaminase (AST)、alkalinephosphatase (AKP)、TBA, hyaluronic acid (HA)、laminin(LN)、Procollagen-III(PIIINP)、superoxide dismutase(SOD)、malondialdehyde (MDA) etc。The hepatic tissues were taken toconduct HE, Masson Staining and test TGF-β1by immunohistochemical method。Theprotein expression level of NOX4、AKT、TGF-β1、α-SMA and AMPK was also detected inthe research。Results:1. Solid dispersion was effective in the protection of BDL rats：It could reducethe levels of ALT, AST and AKP in the rats’ blood serum，and it could also reduce the levelof TBA in the blood serum。Besides。the levels of HA、LN、PIIINP were reduced，and thelevel of SOD in the rats’ blood serum was raised。It was shown in HE and Masson Stainingthat solid dispersion was obviously effective in improving the BDL rats’ pathologicalhistologic changes。2. The influence of solid dispersion on protein-related expressions：Solid dispersioncould decrease the expressions of NOX4、AKT、TGF-β1andα-SMA protein in the tissues ofBDL rats，and it could increase the expression of p-AMPK。Conclusion: It is shown in the study that solid dispersion was effective in suppressing the hepatic fibrosis。The hepatoprotective effects of solid dispersion may be related to theimprovement of the body’ s antioxidant ability，the increase of the p-AMPK expression, thedecrease of NOX，the reduction of Intracellular ROS level and the reduction of TGFβ-1expression。...