Therapeutic Effect of Hydrodynamics-Based Delivery of Matrix Metalloproteinase-13 Gene on Thioacetamide-Induced Liver Fibrosis in Rats

Figure 1

Scheme of thioacetamide (TAA) administration and MMP13 delivery. (a) An appropriate concentration of TAA solution was prepared. For the first 12 weeks, rats in all groups were fed TAA solution. TMT and TMO rats were hydrodynamically injected with MMP13 immediately after 12 weeks of TAA exposure. For the next week, all of the rats (those who received MMP13 injections and those who did not) were fed water without TAA. The rats were fed TAA solution or water for the last 7 weeks depending on their group (rats in the TMT and TOT groups were fed TAA solution, and rats in the TMO and TOO groups were fed water). After euthanasia, liver samples were collected in week 20. T12w rats: rats fed TAA solution for 12 weeks; TMT group: rats fed TAA solution for 12 weeks, injected with MMP13 immediately thereafter, fed water the following week, and again fed TAA solution for the last 7 weeks; TOT group: rats fed TAA solution for 12 weeks, fed water the following week, and again fed TAA solution for the last 7 weeks; TMO group: rats fed TAA solution for 12 weeks, injected with MMP13 immediately thereafter, and fed water up to week 20; TOO group: rats fed TAA solution for 12 weeks and fed water (i.e., no MMP13 injection or additional feeding with TAA solution) up to week 20. (b) Body weight distribution over time and (c) TAA concentration. A suitable concentration of TAA solution was prepared. TAA solution was fed to rats in all groups for the first 12 weeks. The TAA concentration and initial body weight range were 0.03% and 200–230 g, respectively. The TAA concentration was adjusted weekly based on weight change, with the goal of achieving a body weight of  g. For the following 1 week, each rat (whether or not it had received gene therapy) was fed water. For the last 7 weeks, the rats were fed TAA solution or water according to their groups (the TMT and TOT groups were fed TAA solution, while the TMO and TOO groups were fed water). Values are expressed as (SD).

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