The Effect Of Zhiganshengbai Granula On Albumin And Its Mechanism In Experimental Hepatic Fibrosis Rats

Hepatic fibrosis is not an independent disease, but a common pathology alteration of chronic hepatic disease. Chronic hepatic diseases caused by different pathogenies and hepatic hurt led by factors which can damage liver will possibly result in necrosis of liver cells and inflammation and then come into hepatic fibrosis. Hepatic fibrosis means extracellular matrix (ECM) synthesizes more and decomposes less when the liver cells necrose and the inflammation stimulates, and dynamic balance breaks, and then extra ECM deposits in the liver, causing fibrous connective tissue abnormally sedimentates. The mild one is called hepatic fibrosis. If it goes on, hepatic lobules will rebuild its construction and notho-lobules as well as tuber comes into being, and then it is called liver cirrhosis. Clinical and empirical study have confirmed that the hepatic fibrosis can be reversed , but the liver cirrhosis can't. So how to decrease or convert hepatic fibrosis is one of important strategies to cure every kind of chronic hepatic diseases.Most of chronic hepatic diseases such as chronic hepatitis and liver cirrhosis will cause olig-albuminemia and is difficult to retrieve. Traditional treatment is to supply plasma-albumin or plasma blood discontinuously, to step up albumin with western medicine, to enhance high protein diet and so on. But it costs too much or causes poison and secondary reaction,.So, investing the medicine that can step up albumin effectively has a very important value. But the western medicine treatments often focus on one single bit or target, and are difficult to reach the view of healing hepatic fibrosis completely. While, the traditional Chinese medicine has thepredominance of operating on several target sites, and the compound traditional Chinese medicine particularly has the advantages of more channels, more multistratas, more targets to oppose hepatic fibrosis.The Zhiganshengbai Granula is composed of Panax ginseng C.A.Meyer, Scrophularia, Rehmannia glutinosa libosch, Radix paeoniae rubra, Polygonummultiflorum Thunb, panax notoginseng, nutgrass galingale rhizome and so on. Through the experimental hepatic fibrosis rats established by hypodermic injection CCl4 and arachis oil solution, and then introgastric-infused with Zhiganshengbai Granula 2, 4, 8 g/kg respectively. Four weeks later, compared with non-hepatic fibrosis rats(normal comparison group and solvent comparison group), and hepatic fibrosis model group and positive medicine group (Malotilate, 0.1g/kg), we studied the effect of Zhiganshengbai Granula on albumin (ALB), globulin (GLO) and A/G. We also observed the effect of Zhiganshengbai Granula to the lever of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, the content of malonaldehyde (MDA), superoxide dismutase (SOD) and glutathion (GSH) in liver .In the same time, we determined the impact of Zhiganshengbai Granula on the content of nitrogen monoxidum (NO) in serum, the activity of hepatic nitricoxide synthase (NOS) and the content of hepatic hydroxyproline (Hyp). We approached that whether the Zhiganshengbai Granula can convert the abnormality of protein in serum caused by hepatic fibrosis, whether it is beneficial to the prevention and treatment the olig-albuminemia caused by hepatic fibrosis and whether it can resist hepatic fibrosis.When hepatic fibrosis happens, the albumin decreases while the globulin increases and the ratio of A/G steps down or even upsides down. So, theconcentration of serum albumin become very important clinical index to reflect the actual hepatic function and the therapeutic effect. The increase of transaminase in serum could reflect the damage extent of hepatic cells. The more it increases , the more serious it will be. The result indicates that middle dose and large dose of Zhiganshengbai Granula can markedly increase the serum ALB and step up A/G,markedly degrade the serum GLO and markedly depress the activity of serum AST and ALT. It implies that Zhiganshengbai Granula may effectively improve the liver function by promoting the synthesis of protein and preventing hepatic cells from neorobiosis.As the liver is damaged,the capability of liver to create oxyradical unusually increases or the capability of clearing up it decreases, or both of them happen, will lead to oxidative damage of hepatic issue and cells. MDA can reflect the degree of oxidizing reaction, and indirectly reflect the degree of injury of cells. SOD can clean up the superoxide anion radical, decrease the production of MDA, prevent the cells from oxidative damage, and indirectly inflect the capability of organism cleaning up oxyradical. GSH is an important factor to measure the organism ability of antioxidation and it can decrease the peroxidize capability of poison by oxidation-reduction reaction. The experimental results indicate that Zhiganshengbai Granula can markedly decrease the content of MDA in hepatic issue, and markedly increase the activity of SOD and the content of GSH. So, it hints that Zhiganshengbai Granula has antioxidation.When hepatic fibrosis happens, collagen protein can reversibly deposit in the cells space as extracellular matrix. While, hydroxyproline (Hyp) is the special element of collagen protein, and its content can reflect the degree ofcollagen metabolism and hepatic fibrosis. The results manifest that Zhiganshengbai Granula large dose group can markedly decrease the content of Hyp in hepatic issue. It hints that Zhiganshengbai Granula can inhibit the collagen fibers synthesize and deposit.With the existence of NOS, NO is formed by the part of the substrates of L-2-amino-5-guanidinovaleric acid and reduced coenzymeâ…¡(NADPH). NO can react with superoxide anion as free radical, and generate nitroso- peroxide(ONOO-), the latter easily breaks into NO2- and OH- in the meta acid environment, and it has fairly strong oxidation ability to form damaging effect. When hepatic fibrosis happens, the level of NO increases, and it aggravates the hepatic cells inflammation and damage which makes hepatic cells diffuse degeneration and necrosis, and then collagen fibers in zone of necrosis increase, leading to hepatic fibrosis. The result indicates that, compared with solvent control group, the activity of NOS in rats'hepatic issue of the model group markedly increase, as well as the content of serum NO. Zhiganshengbai Granula can degrade the activity of NOS in hepatic issue and the content of serum NO, and it presents invariably dose-dependent relationship. It hints that Zhiganshengbai Granula can inhibit the activity of NOS in hepatic issue and decrease the content of serum NO, and it can, to some extent, improve the liver microcirculation, and relieve the impaired effect of free radical.To sum up, the large dose group Zhiganshengbai Granula can markedly step up the content of hepatic fibrosis serum ALB and the ratio of A/G, and markedly step down the content of serum GLO. It can also depress the activity of serum ALT and AST, as well as decrease the production of Hyp inhepatic issue. It can markedly degrade the content of MDA in hepatic issue and markedly increase the activity of SOD and the content of GSH. It can decrease the activity of NOS in hepatic issue and the content of serum NO, but the effects are not marked.