Effect of lactulose on establishment of a rat non-alcoholic steatohepatitis model

To explore the relationship between changes of intestinal environment and pathogenesis of non-alcoholic steatohepatitis (NASH).

Forty-two Sprague-Dawley rats were randomly divided into model group (n = 24), treatment group (n = 12), and control group (n = 6). The rats of model and treatment groups were given high-fat diet, and those of the control group were given normal diet. Furthermore, the rats of treatment group were given lactulose after 8 wk of high-fat diet. Twelve rats of the model group were killed at 8 wk of high-fat diet. At the 16 wk the rats of treatment group, control group, and the rest of the model group were killed. The serum levels of aminotransferase were measured and the histology of livers was observed by H and E staining.

The livers of rats presented the pathological features of steatohepatitis with higher serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the model group after 16 wk. Compared to the model group, the serum levels of ALT and AST in treatment group decreased significantly and were close to the normal group, and the hepatic inflammation scores also decreased markedly than those in the model group after 16 wk (5.83+/-2.02 vs 3.63+/-0.64, P<0.05), but were still higher than those in the model group after 8 wk (3.63+/-0.64 vs 1.98+/-0.90, P<0.05). However, the degree of hepatic steatosis had no changes in treatment group compared to the model group after 16 wk.

Lactulose could ameliorate the hepatic inflammation of rats with steatohepatitis induced by fat-rich diet, but could not completely prevent the development of steatohepatitis. It is suggested that intestinal environmental changes such as intestinal bacteria overgrowth, are one of the important factors in the pathogenesis of NASH.