Protease inhibitor refers to drugs being capable of inhibiting the activity of proteolytic enzymes to play a role of anti-shock. Proteolysis is an important pathological phenomenon of shock as well as a possible mechanism of the large-scale cell injury during the process of shock and may be related to shock-induced death. Accordingly, it is proposed that protease inhibitor may do well in the prevention of the occurrence and development of shock. Currently the most studied anti-peptide is aprotinin. The possible mechanism of its protective effect on the shock may be as follows:
① prevent the release of plasmakinin;
② inhibition of the activity of the enzymes affecting the capillary endothelial integrity;
③ prevent local edema;
④ inhibit the release and the effect of the lysosomal enzymes;
⑤ prevent the formation of the myocardial depressant factor (MDF).
There is certain difficulty to clinically confirm the above effects with the effect also remaining not quite clearly, and thereby it still demands a lot of research.

Commonly used protease inhibitors
chymotrypsin inhibitor, trypsin inhibitor, pepsin inhibitor, serine protease inhibitors, serine, cysteine protease inhibitors, EDTA (metalloprotease inhibitors) and PMSF (the irreversible inhibitor of serine protease; it is very unstable in an aqueous solution and should be added just before administration). Concentration: PMSF 0.1 mg/ml, Aprotinin 1 µg/ml and Leupeptin: 1 µg/ml (both under the working concentration).

Plant protease inhibitors
Plant Protease inhibitors are a kind of polypeptide substances that widely presented in the plant tissue with defensive effect against many insects. The gene has a relative small coding region and contains no introns. Studies have shown that these protease inhibitors play a very important role in the natural defense system for fighting against harmful insects and pathogens infection in the plants. Insect feeding experiments found that certain purified protease inhibitors have obvious anti-insect effect. The application of protease inhibitor-coding genes to increase insect resistance of plants has become a hot field of plant genetic engineering. There have been found of three types of protease inhibitors in the plants: serine protease inhibitors, thiol protease inhibitors and metalloproteinase inhibitors.
Wherein the study on the serine protease inhibitor is most thorough. It has been currently identified of at least six families of serine protease in the plant in which the arc bean trypsin inhibitor and potato proteinase inhibitor potato are of the best insect resistance. The insecticidal mechanism of protease inhibitors lies in that: it can interact with the digestive enzymes in the gastrointestinal tract of the insects to form a complex (of El) to block or decrease the proteolysis effect of the digestive enzymes. Therefore, once the insect feeds into the protease inhibitors, the normal digestion of foreign proteins will be affected while protease inhibitors and digestive enzymes can form El complexes and stimulate the excessive secretion of digestive enzymes, and cause insect anorexia reaction through the nervous system feedback. Since protease inhibitors inhibit the eating and the digestive process of the insects, it will inevitably lead to a lack of insect metabolism of essential amino acids, eventually leading to abnormal development or death of insects.

Proteasome inhibitor
Proteasome is a multi-subunit macromolecular complex and is widely distributed in the cytoplasm and nucleus of the eukaryotic cells. It is a kind of proteasome complex having multiple catalytic functions and can participate into the degradation of intracellular proteins.
Proteasome inhibitors can suppress the tumor growth, spread, and angiogenesis, and can further cause apoptosis through blocking NF-κB activation.
Bortezomib (PS341) is dipeptide boronic acid protease inhibitors and can induce apoptosis in various tumor cell lines and other cancer cells. It can significantly enhance the efficacy of irinotecan, gemcitabine, doxorubicin and other chemotherapeutic drugs and ionizing radiotherapy in inducing the apoptosis effect of tumor cells. Its proteasome inhibition effect is reversible.
Lactacystin is a selective inhibitor of the 20S proteasome and is the natural metabolite of Streptomyces. It is capable of irreversibly binding to the proteasome to inhibit proteasome activity.
MG132 is a kind of reversible peptide aldehyde proteasome inhibitors and can inhibit the activity of the 26S proteasome, leading to cell cycle arrest in the G2-M phase as well as inhibiting proliferation and inducing apoptosis in a dose-dependent manner.