Application of Nrf2 activator to preparation of anti-artificial joint wear particle induced osteolysis drug

Abstract

The invention discloses an application of an Nrf2 activator to preparation of an anti-artificial joint wear particle induced osteolysis drug. Researches show that artificial joint wear particles can inhibit expression of a cell kernel factor E-2-related factor 2 (Nrf2), and reduce activity of an anti-oxidation reaction element (ARE) regulated and controlled by the downstream of the Nrf2, reduced capacity of controlling an oxidation-reduction reaction in a cell causes active oxygen (ROS) and a lipid peroxidation product malondialdehyde (MDA) in osteoblast to be increased, so that the ROS generation and degradation homeostasis is disordered, the activity of the osteoblast is inhibited, and the balance between osteoclast and the osteoblast is broken. After the Nrf2 activator Oltipraz is added, the content of the ROS in cells can be obviously reduced, and the generation of the lipid peroxidation product MDA is inhibited. In addition, a mouse skull dissolution model is established by implanting CoCrMo nano wear particles under the skin of a mouse skull, effective intervention is applied by intraperitoneal injection of Oltipraz, and in-vivo experiments further prove that the Oltipraz has a remarkable inhibition effect on osteolysis induced by the artificial joint wear particles.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of an Nrf2 activator in the preparation of anti-artificial joint wear particle-induced osteolysis drugs. Background technique [0002] Artificial joint replacement is one of the important methods for the treatment of advanced osteoarthritis, and has achieved good short-term and long-term effects. However, periprosthetic osteolysis after artificial joint replacement is still a major problem for clinicians. During the long-term use of the artificial joint prosthesis, wear particles (such as titanium, polyethylene, ceramics, etc.) will be produced, and these wear particles will gather on the boundary membrane between the bone and the prosthesis, stimulating various tissues around the prosthesis. Inflammatory reaction leads to enhanced osteoclastosis and weakened bone, leading to an imbalance between bone resorption and osteogenesis, and aseptic loosening of artif...

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Problems solved by technology

[0005] Chinese patent document CN112535684A discloses that Oltipraz can reduce the expression level of ROS in photodamaged fibroblasts caused by ultraviolet rays through the Nrf2 pathway, that is, it plays an important role in skin ultraviolet protection and anti-photodamage, but it is not effective in artificial joint wear particles-induced osteolysis. The mechanism of action is still unclear

However, there is no report about the application of the Nrf2 activator Oltipraz of the present invention in the preparation of anti-artificial joint wear particles to induce osteolysis.

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