Protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis

Abstract

Aim: To investigate the protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis (SAP).

Methods: One hundred and eighty SD rats were randomly assigned to the model group, Baicalin-treated group, octreotide-treated group and sham operation group. The mortality, plasma endotoxin level, contents of blood urea nitrogen (BUN), creatinine (CREA), phospholipase A2 (PLA2), nitrogen monoxide (NO), tumor necrosis factor (TNF)-alpha, IL-6 and endothelin-1 (ET-1) in serum, expression levels of renal Bax and Bcl-2 protein, apoptotic indexes and pathological changes of kidney were observed at 3, 6 and 12 h after operation.

Results: The renal pathological changes were milder in treated group than in model group. The survival at 12 h and renal apoptotic indexes at 6 h were significantly (P<0.05) higher in treated group than in model group [66.67% vs 100%; 0.00 (0.02)% and 0.00 (0.04)% vs 0.00 (0.00)%, respectively]. The serum CREA content was markedly lower in octreotide-treated group than in model group at 3 h and 6 h (P<0.01, 29.200+/-5.710 micromol/L vs 38.400+/-11.344 micromol/L; P<0.05, 33.533+/-10.106 micromol/L vs 45.154+/-17.435 micromol/L, respectively). The expression level of renal Bax protein was not significantly different between model group and treated groups at all time points. The expression level of renal Bcl-2 protein was lower in Baicalin-treated group than in model group at 6 h [P<0.001, 0.00 (0.00) grade score vs 3.00 (3.00) grade score]. The Bcl-2 expression level was lower in octreotide-treated group than in model group at 6 h and 12 h [P<0.05, 0.00 (0.00) grade score vs 3.00 (3.00) grade score; 0.00 (0.00) grade score vs 0.00 (1.25) grade score, respectively]. The serum NO contents were lower in treated groups than in model group at 3 h and 12 h [P<0.05, 57.50 (22.50) and 52.50 (15.00) micromol/L vs 65.00 (7.50) micromol/L; P<0.01, 57.50 (27.50) and 45.00 (12.50) micromol/L vs 74.10 (26.15) micromol/L, respectively]. The plasma endotoxin content and serum BUN content (at 6 h and 12 h) were lower in treated groups than in model group. The contents of IL-6, ET-1, TNF-alpha (at 6 h) and PLA2 (at 6 h and 12 h) were lower in treated groups than in model group [P<0.001, 3.031 (0.870) and 2.646 (1.373) pg/mL vs 5.437 (1.025) pg/mL; 2.882 (1.392) and 3.076 (1.205) pg/mL vs 6.817 (0.810) pg/mL; 2.832 (0.597) and 2.462 (1.353) pg/mL vs 5.356 (0.747) pg/mL; 16.226 (3.174) and 14.855 (5.747) pg/mL vs 25.625 (7.973) pg/mL; 18.625 (5.780) and 15.185 (1.761) pg/mL vs 24.725 (3.759) pg/mL; 65.10 (27.51) and 47.60 (16.50) pg/mL vs 92.15 (23.12) pg/mL; 67.91+/-20.61 and 66.86+/-22.10 U/mL, 63.13+/-26.31 and 53.63+/-12.28 U/mL vs 101.46+/-14.67 and 105.33+/-18.10 U/mL, respectively].

Conclusion: Both Baicalin and octreotide can protect the kidney of rats with severe acute pancreatitis. The therapeutic mechanisms of Baicalin and octreotide might be related to their inhibition of inflammatory mediators and induction of apoptosis. Baicalin might be a promising therapeutic tool for severe acute pancreatitis.

Figure 1

Light microscopic changes of kidney (HE, ×400). A: 3-h model group showing protein cast in renal tubule; B and C: 6-h model group showing scattered degenerative necrosis in renal tubular epithelial cells, and renal interstitial edema, respectively; D: 12-h model group showing visible red cell cast.

Figure 2

Bax expression in different groups (×200). A: 12-h model group showing high (+++) Bax expression; B: 3-h Baicalin-treated with negative (-) Bax expression; C: 12-h model group showing moderate (++) Bax expression; D and E: 6-h octreotide-treated group showing mild (+) Bax expression.

Figure 3

Bcl-2 expression in different groups (× 200). A and B: 6-h model group showing high (+++) Bcl-2 expression; C: 6-h octreotide-treated group with negative (-) Bcl-2 expression.

Figure 4

Apoptosis in different groups (TUNEL, × 400). A: 6-h octreotide-treated group showing apoptosis of renal tubular epithelial cells; B: 6-h Baicalin-treated group showing apoptosis of renal tubular epithelial cells; C: 6-h model group with no (-) apoptosis; D: 6-h octreotide-treated group showing apoptosis of renal tubular epithelial cells.