Abstract:

Objective To investigate the production of H₂S and its protective role against mitochondrial dysfunction in rats with nonalcoholic steatohepatitis(NASH). Methods Twenty-six male Spague-Dawlay rats were randomly divided into 3 subgroups: normal group(n=6), NASH model(n=10), and compound fetal bovine liver extract treatment group(n=10). The NASH model was established by feeding rats with high fat diet for 12 weeks. The rate of production of H₂S was detected by methylene blue spectrophotometry and CSE mRNA was tested using RT-PCR. The mitochondrial morphology was assessed by transmission electron microscopy and the fragment of mtDNA, ND₁, ND₆, CO₁, CYB and ATP₆ were respectively tested by PCR. The hepatic steatosis and inflammation were evaluated using HE and Oil Red staining. Results In NASH rats, the hepatic tissue showed diffuse hepatic steatosis as lipid vacuolar degeneration with inflammatory cell infiltration, and the mitochondria showed swelling, becoming round, markedly abnormal morphology. The rate of liver production of H₂S in NASH rats was(1.26±0.08)nmol/min，which was significantly lower than that〔(2.11±0.17) nmol/min〕 in normal group(P<0.05). No significant difference in H₂S production between normal and treated group was observed. The decreased hepatic CSE mRNA and its protein were also observed. The level of mtDNA fragment, ND₁, ND₆, CO₁, CYB and ATP₆ in NASH rats were decreased. Conclusion The decreased hepatic H₂S production and CSE mRNA may be related to mitochondrial injury in NASH rats. Endogenous H₂S may play a beneficial role in pathogenesis of NASH.

Key words: nonalcoholic steatohepatitis, mitochondrial DNA, hydrogen sulfide, cystathioniniyase