| Objective: Alcoholic liver disease is a kind of hepatic lesion which is induced by chronical ingesting bulk of wine or liquor,and it is the most hackneyed hepatopathy in western countries. The incidence of alcoholic fatty liver is growing along with the increase of our national economy.Important pathogenesy of alcoholic liver disease is that massive free radicle and active oxygen can induce lipid peroxidation, protein oxidation, DNA damage, bulky adducts form in the metabolic process of alcohol.Nitric oxide(NO), generated by nitric oxide synthase (NOS) catalysing L-arginine and reacting with oxygen, is a kind of active factor which participate in oxidative stress through diverse paths, further to induce change in hepatic function and morphological. Study reported that NO which has cytotoxicity and can aggravate alcoholic hepatic injury generated by acti- veting inducible nitric oxide synthase (iNOS).Professor Li Dian Gui firstly introduced Zhuo du doctrine by summarizing predecessor theories and bonding many years clinical experience. Zhuo Du is pathoproduction such as tan zhuo, stagnated blood, shui shi and so on. Tan, shi, yu, du zheng are hackneyed by clinical observating in alcoholic liver disease. The experiment aims to investigate the therapeutical effects of hua zhuo jie du decoction and probalble mechanism of action in alcoholic liver disease rats by detecting the expressive level of iNOS, content of malondialdehyde (MDA) and activity of hem- ocuprein (SOD).Method: Forty health male Spague-Dawlay(SD) rats weighted 220～250g were randomly divided into five groups: common group, model group, tiopronin group, chinese materia medica low-dose group and chinese materia medica high-dose group. Common group were given 2ml isotonic Na chloride twice a day by intragastric administration for 12 weeks. The other quadruplet were given liquor of Er Guo Tou of Hong Xing brand by intragastric administration twice a day, the initial concentration was 30%(V/V), ethanol dosage was 5 g·kg-1·d-1, then the concentration of liquor was enhanced by 5%(V/V) and the dosage of ethanol was enhanced by 0.5g/kg weekly, the maxlmum concentration was 60% (V/V) and the maxlmum dosage of ethanol reached up to 8 g·kg-1·d-1. After 8 weeks, tiopronin group, chinese materia medica low-dose group and chinese materia medica high-dose group were given medicine by intragastric administration once daily at noon. The dosage of chinese materia medica given to the chinese materia medica low-dose group was 16.3 g·kg-1·d-1. The dosage of the chinese materia medica high-dose group was 48.9 g·kg-1·d-1 and the dosage of tiopronin given to the tiopronin group was 50 g·kg-1·d-1. After 12 weeks ,we detected the contents of alanine transaminase (ALT),aspartate aminotransferase (AST),alkali phosphatase (ALP),γ-glutamyltransferase (γ-GT),triglyeride (TG),cholesterol total (CHO) in serum by enzymic method, detected the contents of malondialdehyde(MDA)and the activity of superoxide dismutase (SOD) in serum by thiobarbituric acidi(TBA) and xanthine oxidase, observed change in pathology of hepatic tissue by hematoxylin eosin stain, detected the expressive level of inducible nitric oxid synthase (iNOS)in hepatic tissue by the method of immunohistochemistry, and then analyzed images by image analysator (HPIAS-1000) to get average absorption factor ased relative amount of iNOS.Result:1 observation of general state of health: in common group, all the rats were weight gained and agile, color pattern of the rats were mooth and glossy; in model group, the rats was gloomy color pattern, clumsy reaction, nonappetite, noncoagul- ative stool,conjunctival congestion,irritability and weight descend; in tiopronin group, chinese materia medica low-dose group and chinese materia medica high-dose group, the symptomes of rats were lighter compared with model group. General states of chinese materia medica high-dose group were better than tiopronin group and chinese materia medica low-dose group. There was no statistical significance between chinese materia medica low-dose group and tiopronin group.2 The result of biochemical indicator:Compared with common group , all the biochemical indicator of model group remarkably step up(ALT: 109.63±33.32 U/L vs 55.25±10.25 U/L, P<0.05; AST: 295.13±16.18 U/L vs 93.75±15.85 U/L, P<0.05; ALP: 230.13±33.04 U/L vs 99.57±29.31 U/L, P<0.05;γ-GT: 17.63±2.39 U/Lvs10.25±1.48 U/L, P<0.05; TG: 1.48±0.12 mmol/L vs 0.55±0.12 mmol/L, P<0.05;CHO: 2.04±0.34 mmol/L vs 1.19±0.23 mmol/L, P<0.05).Compared with model group,except for ALP, the other biochemical indicator of tiopronin group remarkably stepped down(ALT: 72.37±14.46 U/Lvs109.63±33.32 U/L, P<0.05; AST: 240.75±14.63 U/Lvs295.13±16.18 U/L, P<0.05;γ-GT: 12.87±4.67 U/Lvs17.63±2.39 U/L, P<0.05; TG: 1.04±0.01 mmol/L vs 1.48±0.12 mmol/L, P<0.05;CHO: 1.74±0.14 mmol/L vs 2.04±0.34 mmol/L, P<0.05).Compared with model group,the contents of ALT,AST,ALP in serum of chinese materia medica low-dose group remarkably step down(ALT:88.12±11.05 U/L vs 109.63±33.32 U/L P<0.05; AST: 245.63±56.59 U/L vs 295.13±16.18 U/L, P<0.05; ALP: 191.50±34.69 U/L vs 230.13±33.04 U/L, P<0.05),the descendent degree of other biochemical indicator didn,t have statistical significance.Compared with model group,all the biochemical indicator of chinese materia medica high-dose group remarkably stepped down(ALT: 74.88±17.48 U/L vs 109.63±33.32 U/L, P<0.05; AST: 205.36±47.04 U/L vs 295.13±16.18 U/L, P<0.05; ALP: 159.14±18.95 U/Lvs230.13±33.04 U/L, P<0.05;γ-GT: 12.05± 3.27 U/L vs 17.63±2.39 U/L, P<0.05; TG: 0.76±0.21 mmol/L vs 1.48±0.12 mmol/L, P<0.05; CHO: 1.34±0.35 mmol/L vs 2.04±0.34 mmol/L, P<0.05).Compared with chinese materia medica low-dose group,except for AST ALP, the other biochemical indicator of tiopronin group remarkably stepped down(ALT: 72.37±14.46U/Lvs88.12±11.05U/L,P<0.05;γ-GT: 12.87±4.67 U/L vs 16.13±4.29 U/L, P<0.05; TG: 1.04±0.01mmol/Lvs 1.32±0.33 mmol/L, P < 0.05;CHO: 1.74±0.14mmol/L vs 1.98±0.39 mmol/L, P<0.05).Compared with chinese materia medica low-dose group,the biochemical indicator of chinese materia medica high-dose group remarkably stepped down(ALT: 74.88±17.48U/L vs 88.12±11.05 U/L, P<0.05; AST: 205.36±47.04U/L vs 245.63±56.59 U/L, P<0.05; ALP:159.14±18.95U/L vs191.50±34.69 U/L,P<0.05;γ-GT:12.05±3.27mmol/Lvs 16.13±4.29 mmol/L, P<0.05; TG: 0.76±0.21mmol/Lvs 1.32±0.33 mmol/L, P<0.05; CHO: 1.34±0.35 mmol/L vs1.98±0.39mmol/L, P<0.05).Compared with tiopronin group,except forALT,γ-GT, the other biochemical indicator of chinese materia medica high-dose group remarkably stepped down(AST: 205.36±47.04 U/L vs 240.75±14.63 U/L, P<0.05; ALP: 159.14±18.95 U/L vs 221.57±31.98U/L, P < 0.05;TG: 0.76±0.21 mmol/Lvs1.04±0.01 m mol/L,P<0.05; CHO:1.34±0.35 mmol/Lvs 1.74±0.14 mmol/L, P<0.05).3 The result of the contents of malondialdehyde (MDA)and the activities of superoxide dismutase(SOD) in serum.Compared with common group,the contents of MDA in serum of the other quadruplet stepped up at aniso-level(model group:19.06±1.70 umol/L vs 7.18±1.37 umol/L, P < 0.05; tiopronin group:10.35±2.32 umol/L vs 7.18±1.37 umol/L, P<0.05; chinese materia medica low-dose group:13.06±1.45 umol/L vs 7.18±1.37 umol/L, P<0.05; chinese materia medica high-dose group:10.73±1.01 umol/L vs 7.18±1.37 umol/L, P<0.0 1).Compared with model group,the contents of MDA in serum of tiopronin group, chinese materia medica low-dose group, chinese materia medica high-dose group all stepped down.(tiopronin group: 10.35±2.32 umol/L vs 19.06±1.70 umol/L , P<0.05; chinese materia medica low-dose group: 13.06±1.45 umol/L vs 19.06±1.70 umol/L, P<0.05; chinese materia medica high-dose group: 10.73±1.01 umol/L vs 19.06±1.70 umol/L, P<0.05).The contents of MDA in serum of chinese materia medica high-dose group, tiopronin group were lower than chinese materia medica low-dose group group(tiopronin group: 10.35±2.32 umol/L vs 13.06±1.45 umol/L , P<0.05; chinese materia medica high-dose group:10.73±1.01 umol/L vs 13.06±1.45 umol/L, P<0.05);There was no statistical significance between chinese materia medica high-dose group and tiopronin group.P>0.05.Compared with common group,the activities of SOD in serum of the other quadruplet stepped down at aniso-level (model group: 117.23±10.16 U/ml vs 186.15±9.92 U/ml, P<0.05; tiopronin group:137.38±14.94 U/ml vs186.15±9.92 U/ml, P<0.05; chinese materia medica low-dose group:131.88±10.21 U/ml vs 186.15±9.92 U/ml, P<0.05; chinese materia medica high-dose group:153.83±15.27 U/ml vs 186.15±9.92 U/ml, P<0.05).Compared with model group,the activities of SOD in serum of tiopronin group, chinese materia medica low-dose group, chinese materia medica high-dose group all stepped down were higher.(tiopronin group:137.38±14.94 U/ml vs117.23±10.16 U/ml, P < 0.05; chinese materia medica high-dose group: 131.88±10.21 U/ml vs117.23±10.16 U/ml, P<0.05; chinese materia medica low-dose group:153.83±15.27 U/ml vs117.23±10.16 U/ml, P<0.05).Compared with chinese materia medica high-dose group, the activities of SOD in serum of tiopronin group,chinese materia medica down-dose group were lower(tiopronin group:137.38±14.94 U/ml vs 153.83±15.27 U/ml, P<0.05; chinese materia medica low-dose group:131.88±10.21 U/ml vs 153.83±15.27 U/ml, P<0.05)There was no statistical signific- ance between chinese materia medica low-dose group group and tiopronin group P>0.05.4 The detected result of histopathology of hepatic tissue: Characteristie of histology of hepatic tissue of the rats in the common group was integrity hepatic lobules,regular liver model group,the characteristie of histology of hepatic tissue were disappeared hepatic lobules,midrange steatosis,greate and oncotic liver cell,stenochoria sinus hepaticus companied with inflammatory cell infiltrate,punctiform cellular necrosis focus. the size of intracytoplasm lipid droplet is unevenness, little lipid droplet is at most. In the chinese materia medica low-dose group and tiopronin group, the degree of steatosis of the rats , inflammatory cell infiltrate and liver neorobiosis are stepped down; In the chinese materia medica high-dose group, the characteristie of histology of hepatic tissue of the rats was integrity hepatic lobules, regular liver cell cord and lower grade limitations steatosis,and the degree of inflammatory cell infiltrate were the lowest.5 The detected result of iNOS of hepatic tissue:In common group, iNOS of hepatic tissue didn,t express; The average absorption factor of hepatic tissue of model group remarkably step up at the twelfth weekend(53.30±10.03,P<0.05); The average absorption factor of hepatic tissue of tiopronin group,chinese materia medica low-dose group and chinese materia medica high-dose group stepped up too at aniso-level(39.54±5.30,28.52±7.90,23.70±2.93); The average absorption factor of hepatic tissue of chinese materia medica high-dose group was lowest than chinese materia medical low-dose group and tiopronin group,(P<0.05); there was no statistical significance between chinese materia medica low- dose group and tiopronin group.Conclusion:1 The Hua Zhuo Jie Du decoction can remarkably improve the biochemical indicator in serum and histopathology in alcoholic liver disease . Therapeutical effect of Hua Zhuo Jie Du decoction is significant. Therapeutical effect of chinese materia medica high-dose group is better than tiopronin group.2 The effective mechanism that Hua Zhuo Jie Du decoction has a significant therapeutical effect on alcoholic liver disease in rats may relate with depressing the contents of MDA, enhancing the activities of SOD in serum and restraining expression of iNOS in hepatic tissue3 Our study proved that the zhuo du nei yun may be the important pathogenesy of Alcoholic liver disease in Chinese traditional medicine.
|
PDF Full Text Request