Study On The Lipid Lowering Effect And Mechanism Of Chitosan And The Relatesd Products

As a type of systemic and abnormal lipids metabolic disease that damages the humanhealth, hyperlipidemia has been considered as one of the leading risk factors for cardiovas-cular and cerebrovascular diseases. With the transformations of the modern diet-and life-styles, hyperlipidemia has become one of the public health problems all over the world. Asthe primary treatment for hyperlipidemia, the chemotherapies present various adversereactions (ADRs). It’s necessary for hyperlipidemia to explore the natural lipid-loweringdrugs characterized by safety, effectivity and less ADRs at present.Chitosan (CTS), the only positive alkaline polysaccharide extracted from the shrimp orcrab shells and that shows the biocompatibility and nontoxic nature, it has the potentials ofhypolipidemic and weight losing activities. Because that CTS manifests the features of poorwater solubility and it is generally predisposed to the side effects, such as nausea, emesisand constipation.our research group transformed CTS into chitosan microspheres (CTMS)and capsaicin loaded chitosan microspheres (CCMS) presenting good dispersibility andhigh bioavailability, which meet with the aims of enhancing hypolipidemic activity anddepressed ADRs. Chitooligosaccharide II (COSII), chitooligosaccharideI (COSI) andglucosamine (GLC), the degradation products of CTS, also has the characteristics of highwater solubility, superior absorption, and low toxicity.The first aim of the experiment is to evaluate the roles of CTS and related products inthe lipid accumulation in hepatocytes. The capacities of eliminating lipid accumulationwere evaluated from four aspects: the thiazolyl blue dye absorbance (MTT value) forascertaining the safe concentration range, Oil red O staining for observing the morphology of intracellular lipid droplets, the extraction of Oil red O quantified lipids, and determiningthe intracellular triglyceride (TG) contents. The results demonstrated that all of thematerials above can effectively suppress lipid accumulation and reduce dose dependentlythe TG level in hepatocytes.The next step of the experiment is to explore the hypolipidemic activity of CTS and itsdegradation products in high fat diet-induced hyperlipidemic SD rats. The study showedCTS, COSII and GLC can effectively reduce body weight, Lee’s index, visceral index, andfat/body, and suppress the adipocyte growth, suggesting that they have dose dependentweight-losing activities to certain extent. Meanwhile, there exists a lipid-lowering functionof the four materials because that they can significantly decrease the plasmic TC, TG andLDL-C levels, reduce hepatic TC, TG and increase TBA concentrations in liver, as well asimprove the excretion of TC、TG and TBA in rats. Additionally, COSII and GLC presentantioxidation in that they all can enhance SOD enzymatic activity to varying extent, andCTS, COSII and GLC play an important role in liver protection for the reason that they canmarkedly lower AST and ALT levels in serum and liver, as well as remit the symptoms offat liver in rats.To further study their lipid-lowering mechanisms, we detected the influences of CTSand its degradation products on the protein expressions of lipid mechanism-related enzymes,including HL and PPARα proteins, by Western Blotting after HepG2cells characterized byhigh TC and TG levels and suppressive PPARα. The results showed that only CTMS couldsignificantly promote the expressions of HepG2intracellular HL and PPARα proteins withno effects of other materials. Suppressing the expression of PPARα gene can dramaticallyinhibit the expression of HL protein, suggesting that the role of CTMS in promoting theexpression of HL protein associates with PPARα gene. Under the condition of high TC andTG concentration in HepG2cells, CTMS facilitates both the expression of HL protein andthat of PPARα protein and that was disappeared after the inhibition of PPARα gene,indicating that the acceleration of PPARα expression may contribute to the expression ofHL protein.