Abstract:

Objective To investigate the efficacy of rapamycin arterial perfusion combined with ¹³¹I-fibroblast activation protein （FAP） loaded dextran microspheres in the treatment of rabbits with liver transplantation tumor. Methods Fifty male New Zealand white rabbits were selected. Forty white rabbits were used to establish liver transplantation tumor models and were randomly divided into a negative control （based on arterial perfusion with the same volume of normal saline， MO） group， rapamycin arterial perfusion （RA） group， ¹³¹I-FAP loaded dextran microspheres for interventional embolization therapy （IF） group， and rapamycin arterial perfusion combined with ¹³¹I-FAP-loaded dextran microspheres interventional embolization therapy （RI） group by the random number table method， with 10 rabbits in each group. The remaining 10 unmodeled white rabbits were classified as the normal （based on arterial perfusion with the same volume of normal saline， NO） group. The pathological morphology of tumor tissues was detected by HE staining， liver function was detected by automatic biochemical analyzer， apoptosis of tumor cells was detected by TUNEL method， and the protein expression of vascular endothelial growth factor （VEGF） and vascular endothelial growth factor receptor （VEGFR） in liver tissues was detected by Western blotting. Results The tumor mass of MO group， RA group， IF group and RI group was （20.33±2.39）， （14.62±1.23）， （14.34±1.22）， （8.28±0.84） g， respectively. Tumor volumes were （0.87±0.13）， （0.51±0.09）， （0.53±0.08）， （0.32±0.02） cm³， respectively. Tumor necrosis rates were （21.11±2.14）%， （32.18±3.25）%， （32.29±3.28）%， （48.53±4.37）%， respectively. Tumor suppression rates were （0.00±0.00）%， （24.66±2.47）%， （24.13±2.46）%， （45.55±4.51）%， respectively. There were statistically significant differences （F=316.40， P<0.001； F=159.50， P<0.001； F=356.10， P<0.001； F=571.30， P<0.001）； there were statistically significant differences in RA， IF and RI groups compared with the MO group （all P<0.05）； there were statistically significant differences between RI group and IF group （all P<0.05）. Tumor cells of MO group showed infiltrating growth， with more mitotic images， no obvious necrosis， and a large number of inflammatory cell infiltration. Cancer nests in RA group， IF group and RI group became significantly smaller， tumor cells showed swelling， nuclear contraction and a large number of necrosis， and inflammatory cell infiltration was significantly reduced， among which the improvement was most obvious in RI group. The albumin （ALB） level of NO group， MO group， RA group， IF group and RI group was （40.55±4.38）， （17.34±1.02）， （22.65±2.18）， （22.37±2.17）， （29.01±2.83） g/L， respectively. The alanine aminotransferase （ALT） level was （19.68±1.34）， （92.17±9.24）， （78.71±7.39）， （78.35±7.40）， （50.30±5.12） U/L， respectively. The aspartate aminotransferase （AST） level was （74.27±7.48）， （182.21±20.23）， （165.78±16.05）， （165.26±16.09）， （102.33±11.11） U/L， respectively. The total bilirubin （TBIL） level was （22.42±2.58）， （82.24±8.35）， （61.86±6.17）， （61.53±6.16）， （46.45±4.53） μmoL/L， respectively. There were statistically significant differences （F=105.90， P<0.001； F=189.00， P<0.001； F=99.57， P<0.001； F=142.10， P<0.001）； there were statistically significant differences in MO， RA， IF， RI groups compared with the NO group （all P<0.05）； there were statistically significant differences in RA， IF， RI groups compared with the MO group （all P<0.05）； there were statistically significant differences between IF group and RI group （all P<0.05）. The apoptosis rates in MO group， RA group， IF group and RI group were （9.01±1.23）%， （15.65±1.68）%， （15.72±1.69）% and （24.34±2.12）%， respectively， and there was a statistically significant difference （F=135.30， P<0.001）； there were statistically significant differences in RA， IF and RI groups compared with the MO group （all P<0.05）； there was a statistically significant difference between RI group and IF group （P<0.05）. VEGF expression level in NO group， MO group， RA group， IF group and RI group was 1.33±0.13， 2.28±0.21， 1.88±0.19， 1.86±0.18 and 1.50±0.14， respectively. VEGFR expression level was 1.32±0.09， 2.14±0.28， 1.91±0.18， 1.89±0.17， 1.62±0.15， respectively. There were statistically significant differences （F=45.84， P<0.001； F=29.05， P<0.001）； there were statistically significant differences in MO， RA， IF， RI groups compared with the NO group （all P<0.05）； there were statistically significant differences in RA， IF， RI groups compared with the MO group （all P<0.05）； there were statistically significant differences between IF group and RI group （both P<0.05）. Conclusions Rapamycin arterial perfusion combined with ¹³¹I-FAP-loaded dextran microspheres interventional embolization therapy in the treatment of rabbits with liver transplantation tumor can effectively inhibit tumor growth， enhance the tumor necrosis rate， tumor inhibition rate and apoptotic ability， improve liver function indicators， and has a significant therapeutic effect on rabbits with liver transplantation tumor.

Key words: Liver neoplasms, Rabbits, Sirolimus, Embolization， therapeutic