Compound used for treating ischemia reperfusion injuries
A compound and solvate technology, applied in the field of compounds for the treatment of ischemia-reperfusion injury, can solve the problems of high mortality and injury in patients with acute myocardial infarction
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Embodiment 1
[0147] Example 1 The inhibitory effect of ML355 on liver ischemia-reperfusion injury is dose-dependent
[0148] In order to verify the inhibitory effect of different doses of ML355 on liver ischemia-reperfusion injury, C57 mice were randomly divided into 4 groups and injected 1mg / kg ML355 (HY-12341, MCE company), 2mg / kg ML355, 3mg / kg through the tail vein. kg ML355 and solvent (control group, DMSO:Solutol:PEG400:water=5:10:20:65 (v:v:v:v)), and then perform I / R surgery according to the method of the aforementioned liver I / R animal model . At different time points after operation, serum and liver tissue were collected for ALT and AST enzyme activity detection and HE staining.
[0149] The test results of ALT and AST are as follows: Figure 1A , Figure 1B As shown, compared with the solvent control group, after ML355 administration, the ALT and AST contents in the serum of mice were significantly reduced at 6 hours after the operation, and the ALT and AST contents in the ML355 3mg / k...
Embodiment 2
[0151] Example 2 ML355 effectively relieves liver damage caused by ischemia-reperfusion
[0152] In order to study the protective effect of ML355 on liver ischemia-reperfusion at different times, C57 mice were randomly divided into 7 groups, each with 20 mice. Ten mice in each group were given 3 mg / kg of ML355 dissolved in solvent through tail vein injection, and the other ten mice were given solvent. After the administration was completed, 7 groups of mice were subjected to I / R surgery (one group was the Sham control group, and the remaining 6 groups were the I / R experimental group). The Sham control group and the postoperative 0h, 1h, 3h, 6h, 12h, 24h I / R experimental group mouse serum, ALT, AST test to evaluate the degree of liver damage; Sham control group and postoperative 0h, 6h I / R experimental group mouse liver tissues, made paraffin sections, TUNEL Staining, Mac1 immunofluorescence staining and Ly6G immunofluorescence staining to evaluate liver cell apoptosis and liver ...
Embodiment 3
[0157] Example 3 ML355 inhibits ischemia-reperfusion injury in different tissues
[0158] 1. ML355 inhibits cardiac ischemia-reperfusion injury
[0159] C57 mice were randomly divided into 4 groups (Sham group, I / R 6h group, I / R 12h group, I / R 24h group), 7 mice in the Sham group, 15 mice in each of the other 3 groups, of which the I / R group Seven mice were given 3 mg / kg of ML355 dissolved in solvent through tail vein injection, and the other 8 mice and the Sham group were given solvent. After the administration, the 4 groups of mice were subjected to I / R surgery, and the serum of the Sham control group and the I / R experimental group at 6h, 12h, and 24h after the operation were taken for CK and LDH detection to evaluate the degree of cardiac damage.
[0160] The experimental results are as Figure 6A with 6B As shown, the serum levels of CK and LDH increased significantly after I / R. When ML355 was given through the tail vein, the serum CK content was lower than that of the ML355 gr...
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