Berberine inhibits enterocyte apoptosis in septic mice

AIM: To observe the effects of berberine (Ber) on enterocyte apoptosis in septic mice and its possible mechanism. METHODS: Male C57BL/6 mice (8~10 weeks old) were randomly divided into sham group, cecal ligation and puncture (CLP) group, CLP+Ber group and sham+Ber group. The mice in CLP group underwent CLP ope-ration, and the mice in sham groups suffered a similar operation except the ligation and puncture. After the sham or CLP operation, the mice were administered intragastrically with distilled water or berberine (50 mg/kg) within 2 h. After 20 h, the mice were killed with excess pentobarbital sodium and the ileum tissues were removed. The histological changes of the intestine were observed and the enterocyte apoptosis was examined by determining the protein level of cleaved caspase-3. Furthermore, mitochondrial Bax, cytoplasm cytochrome C (Cyt C) and the total proteins of Bcl-2, Fas, FasL and Fas-associated protein with death domain (FADD) were examined by Western blot. The mRNA expression of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) was measured by real-time PCR. RESULTS: The extensive ileum injuries, including remarkably increased leukocytes and necrosis of intestinal villus were observed 20 h after CLP. In CLP group, the protein levels of cleaved caspase-3, cytoplasm Cyt C, as well as Fas, FasL were significantly increased, but the Bcl-2 level was decreased. Bax translocation into mitochondria was promoted. However, FADD was not changed significantly. The mRNA expression of TH and DBH was also increased sharply in CLP group. On the contrary, treatment with berberine made a considerable alleviating alteration in the ileum of the septic mice.CONCLUSION: Treatment with berberine provides protective effects on intestinal injury in septic mice by reducing enterocyte apoptosis, and its possible mechanism may be involved in the inhibition of the endogenous and exogenous apoptosis pathways.