Photodynamic therapy with hematoporphyr in monomethyl ether alleviates venous neointimal hyperplasia in arteriovenous fistulas in rabbits

Abstract

Objective To observe the effects of photodynamic therapy (PDT) with hematoporphyrin monomethyl ether (HMME) on venous neointimal hyperplasia (VNH) in arteriovenous fistulas (AVFs) in rabbits. Methods We established models of AVF by end-to-side anastomosis of the common carotid artery to the jugular vein in 32 adult rabbits, which were randomized into 4 groups (n=8), including a control group without any intervention, an HMME group with HMME treatment only, a light illumination (without HMME) group, and a HMME-PDT group receiving both the photosensitizer and light illumination. Color Doppler ultrasound was used to detect the blood flow after the operation. At 30 d after the operation, the jugular vein tissue was collected for assessing VNH and measurement of the lumen area using HE and Masson staining and for detecting the expression of proliferating cell nuclear antigen (PCNA) and ɑ-smooth muscle actin (ɑ-SMA) using immunohistochemistry; Western blotting was performed to analyze the expression of proliferating cell nuclear antigen (PCNA), Bcl-2, ɑ-SMA, Caspase3, Caspase9 and Bax. Results The jugular vein tissues showed significantly lessened VNH and increased lumen area in HMME-PDT group compared with the other groups (P < 0.05). The results of immunohistochemistry showed that the expression of PCNA and ɑ-SMA was decreased and Caspase3 expression was increased significantly in HMME-PDT group compared with the other groups (P < 0.05). Western blotting results showed that among the 4 groups, the expression of Caspase3, Caspase9 and Bax were the highest (P < 0.05) while those of PCNA, Bcl-2, ɑ-SMA and Bcl-2/Bax ratio the lowest in HMME-PDT group (P < 0.05). Conclusion HMME-PDT can effectively reduce VNH in AVFs in rabbits by suppressing proliferation and promoting apoptosis of the vascular smooth muscle cells via the Bcl-2/Bax pathway.

Keywords

• arteriovenous fistula
• venous neointimal hyperplasia
• photodynamic therapy
• hematoporphyrin monomethyl ether
• apoptosis