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[Dynamic changes of plasma levels of prostacycline and thromboxane A2 and their correlation with the severity of hepatic injury in rats with nonalcoholic fatty liver disease].

OBJECTIVE
To investigate the dynamic changes of plasma levels of prostacycline (PGI2) and thromboxane A2 (TXA2) and their relationship with the severity of hepatic injury in rats with nonalcoholic fatty liver disease (NAFLD).


METHODS
We established a NAFLD model, with a fat-rich diet consisting of 10% lard oil + 2% cholesterol, which was given to Sprague-Dawley rats (n=48) for a period of 8, 12, 16 and 24 weeks. The other rats were fed standard diets and were used as normal controls (n=24). At sacrifice, liver pathology scores were evaluated and plasma levels of PGI2, its stable metabolic product 6-keto-PGF1 alpha and TXA2, and TXB2 were determined by radioimmunoassay.


RESULTS
Simple fatty livers were observed in the model group at 8 weeks. From 12 weeks to 24 weeks, the livers gradually progressed from simple steatohepatitis to liver fibrosis. Plasma levels of TXB2 in the model group increased higher than in the control group after 8 weeks [(52.4+/-3.15) ng/L vs (41.1+/-1.45) ng/L] and continued to increase over time, with the highest levels at 24 weeks [(117.7+/-7.47) ng/L]. A strong positive correlation (r=0.537) was seen between plasma TXB2 levels and the severity of liver injury. Plasma 6-keto-PGF1 alpha concentrations decreased in the model group in comparison with the control group after 8 weeks [(31.1+/-1.62) ng/L vs (36.5+/-1.68) ng/L] and continued to decrease over time, with the lowest concentrations at 24 weeks [(3.4+/-2.43) ng/L t=3.77]. A negative correlation was shown between the 6-keto-PGF1 alpha level and the severity of the liver injury.


CONCLUSION
A rat model of NAFLD was established successfully by feeding a fat-rich diet for 24 weeks. In this model, the imbalance of plasma PGI2 and TXA2 levels (increased TXB2 and decreased 6-keto-PGF1 alpha levels) may play a role in the pathogenesis of experimental NAFLD.