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Therapeutic Effects of Hepatocyte Transplantation by Using HGF Loaded PLA-O-CMC Nanoparticles on Treating Rats with Acute Liver Failure

Author: ChangRenAn
Tutor: ChenZhong
School: Nantong University
Course: Surgery
Keywords: Hepatocyte transplantation Acute liver failure Hepatocyte growth factor Nanoparticles Drug-loaded
CLC: R575.3
Type: Master's thesis
Year: 2008
Downloads: 50
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Abstract


Objective: To observe the carrier hepatocyte growth factor (HGF) the polylactide-O-carboxymethyl chitosan nanoparticles (PLA-O-CMC) in cultured rat hepatocytes intraperitoneal transplantation for acute liver failure (ALF) in rats the therapeutic effect and to explore its mechanism. : D-amino half lactose (D-gal) intraperitoneal injection (1.2g/kg) rat ALF model after 48 hours respectively 5ml (containing 5.0 × 10 ~ 7) conventional collagen rat hepatocytes cultured for 24h (I group), PLA-O-CMC nanoparticles cultured for 24h rat hepatocytes (Ⅱ group), the PLA-O-CMC nanoparticles contained HGF culture 24h rat hepatocytes (III group) transplanted into a rat model 5ml PLA-O-CMC nanoparticles intraperitoneal the culture 24h rat hepatocytes intraperitoneal transplantation plus daily intravenous HGF 10μg/kg × 7d (IV group) and 5ml mixed cell culture medium intraperitoneal injection (Ⅴ group) as controls. Observation receptors in rats 14d survival, liver function, pathological changes of the liver and mitotic index, and hepatocyte ultrastructural changes; observe the pathological changes of transplanted hepatocytes. Immunohistochemical assay receptor liver Ki-67 antigen, proliferating cell nuclear antigen (PCNA) and brominated nucleoside uracil (BrdU) incorporation labeling index. The enzyme-linked immunosorbent assay concentration of HGF receptor serum and liver tissue. The flow cytometry receptor rat liver cell proliferation index, as well as culture and transplanted hepatocytes apoptosis rate and necrosis rate and survival. Results: 14d ALF rat survival rate after transplantation: Ⅰ ~ Ⅴ group were 50.00%, 68.75%, 81.25%, 75.00%, 18.75%. Each transplant group was higher, the difference was statistically significant (P lt; 0.05). 24 hours after transplantation, beginning Ⅱ, Ⅲ, the N group liver function indicators began to improve, compared Ⅴ group difference was statistically significant (P lt; 0.05); most obvious difference transplant 5d III of ALB was significantly higher than the rest groups (P lt; 0.05); to 7 days after transplantation, in each group, in addition to ALT, the difference was not statistically significance (P gt; 0.05). Group Ⅲ liver function and liver the pathological damage restoration fastest, the best, followed by the group Ⅳ II group, Ⅰ group, Ⅴ group to restore the slowest and the worst. Ⅲ group of transplanted hepatocytes survive longer, mild inflammatory infiltration. Group III hepatic lobule structure faster recovery, liver cells under the electron microscope mitotic dense rough endoplasmic reticulum, mitochondria more. The performance of the groups have liver regeneration after transplantation, the transplantation group than the control group, better than the non-nano-nano group group. Group Ⅲ mitotic index, Ki-67, of PCNA of BrdU labeling index, hepatocyte proliferation index are higher than the rest of the group, part-time difference was statistically significant (P lt; 0.05). Serum and liver tissue HGF concentrations were higher in the groups HTx 3d increased the most obvious. Group III liver tissue HGF concentrations higher than the other groups, IV serum HGF concentrations higher than the other groups (P lt; 0.05). With time, the survival rate of liver cells decreased the rate of apoptosis and necrosis rate, the highest survival rate of group III liver cells, the lowest rate of apoptosis. Days after transplantation, the most obvious difference Ⅲ and Ⅳ group living liver cells was significantly higher than that in group Ⅰ and group Ⅲ than group Ⅱ, Ⅲ and group Ⅳ apoptosis rate was significantly lower than that in group Ⅰ, Ⅲ group were lower than group II, the difference was statistically significant (P lt; 0.05). Conclusion: the application upload HGF PLA-O-CMC nano-particles in cultured rat liver cells intraperitoneal transplantation for treatment of D-gal-induced ALF rats significantly reversal of liver function and improve survival; liver regeneration by promoting receptor, inhibiting The transplanted hepatocytes apoptosis, play a better role in the treatment of.

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CLC: > Medicine, health > Internal Medicine > Digestive and abdominal diseases > Liver and gall bladder disease > Liver failure
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