| Background: Nonalcoholic steatohepatitis (NASH) represents anadvanced stage of fatty liver disease that occurs in patients withoutsignificant alcohol consumption. Histologically, it is characterized bymacrovesticular steatosis, periportal and lobular inflammation, Mallorybodies and fibrosis. It is now considered that NASH can progress toadvanced fibrosis and may account for most cases of cryptogenic cirrhosis.Despite its high prevalence, the pathogenesis of this disorder is not wellunderstood. It has been suggested that oxidative stress and resulting lipidperoxidation may play a central role in the pathogenesis of NASH.Cytochrome P-450 2E1 (CYP2E1) involves in the development of NASHas a major microsomal source of oxidative stress. Peroxisomalproliferator-activated receptor alpha (PPARα) has been explored as thekey regulator involved in peroxisomal, mitochondrial and microsomaalfatty acid oxidation system in liver, and defects in PPARα can lead tosteatohepatitis. At present, there is no widely accepted approach to treatNASH. Objective: This study aimed to investigate the efficacy of traditionalChinese medicine-Ganzheng Fang on CYP2E1 and PPARαactivity in ratswith NASH and further to explore the mechanism of Ganzheng Fang. Methods: 30 male Sprague-Dawley rats were divided into threegroups randomly: the controlled group (n=10) were fed with normal diet,the NASH model group (n=10) and the Ganzheng Fang treatment group(n=10) fed with high-fat diet for 16 weeks. Furthermore, the treatmentgroup were given with Ganzheng Fang (10ml/kg rat body weight)simultaneously after 12 weeks of high-fat diet. The ingredients are Chaihu(Radix Bupleuri), Danshen (Radix Salvia Miltiorrhizae), Zexie (RhizomaAlismatis), Banxia (Rhizoma Pinelliae), and Shengshanza (FructusCrataegi). Sixteen weeks later all rats were sacrificed. The diets and waterwere given ad libitum. Seral aminotransferase, seral TG and TC, TG andTC in homogenized liver tissue were detected, the malondialdehyde (MDA)and superoxide dismutase (SOD) activity of hepatic tissue were alsomeasured. The pathology of liver were observed by HE stain. HepaticCYP2E1 and PPARα were detected by immuneohistochemistry usingspecific antibodies. CYP2E1 and PPARα mRNA were assayed withreverse transcriptase-polymerase chain reaction (RT-PCR). Results: 1. Body weight (g) and liver/body weight index: The meanbody weight and liver/body weight index of model group (493.20±19.55and 3.33±0.74%, respectively) were increased significantly comparedwith normal group (371.60±31.69 and 2.89±0.14%, respectively) (P﹤0.01 and 0.05, respectively). Compared with model group, the treatmentgroup (421.80±15.51, 2.97±0.10%) were decreased markedly (P﹤0.01). 2. Pathology observed by HE stain: Steatosis was not seen incontrolled group, while severe lipid degeneration and inflammation of liverwere found in model group (P﹤0.01). Steatosis and inflammation showsignificant improved compared with model group (P ﹤ 0.01). Theinflammation score in model group (6.80 ± 1.32) were increasedsignificantly compared with normal group (0) (P﹤0.01). Compared withmodel group, the treatment group (2.80±1.03) were decreased remarkably(P﹤0.01). 3. immuneohistochemistry: ①In normal group, the percentage ofCYP2E1 immunostaining positive cell was zero; in model group, thepercentage was 70%, which indicated the expression of CYP2E1 proteinwere significantly higher than that in normal group (P=0.002); thepercentage of immunostaining positive cell in treatment group was 20%,which indicated the expression of protein were markedly lower than that inmodel group (P=0.035) and had no statistically difference with normalgroup (P=0.287). ②The number of PPARαpositive cell in model groupwere markedly lower than that in normal group (P﹤0.01), but had nosignificant with difference with treatment group (P﹥0.05). 4. Expression of CYP2E1 and PPARαmRNA: ①The expression ofCYP2E1 mRNA in model group (2.809 ± 0.020) were increasedsignificantly compared with that of normal group (1.199±0.028) (P﹤0.01). Compared with mod... |
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