Objective: To investigate the effects of the pyrin domain-containing
protein 3 (NLRP3)
inflammasome inhibitor
MCC950 on nerve injury in rats with
intracerebral hemorrhage(ICH). Methods: Seventy-two SD rats were randomly divided into three groups (n=24):
Sham group, ICH group and
MCC950 group. ICH group and
MCC950 group rats were injected with autogenous non-
anticoagulant blood to establish ICH model, and then the rats in
MCC950 group were intraperitoneally injected with
MCC950 at the dose of 10 mg/kg(2 mg/ml) for 3 days after ICH model was established. Seventy-two hours after the establishment of the model, the forelimb placement test, the corner test and mNSS score were performed to observe the neurological function of the rats with ICH. The volume of
hematoma was observed in fresh brain tissue sections. HE staining was used to observe the pathological changes of brain tissue. The dry-wet weight ratio was calculated to evaluate the changes of brain tissue
edema. The degeneration of neurons was observed by FJC staining. The neuronal apoptosis was observed by TUNEL staining. The
protein expression and activation levels of NLRP3, ASC, caspase-1, IL-1β,
IL-18 and GSDMD were determined by Western blot. Results: Compared with
sham group, the percentage of successful placement of left forelimb and left turn was decreased significantly (P<0.01, P<0.05), mNSS score was increased significantly (P<0.01) in ICH group.
Hematoma volume was increased significantly, the number of microglial cells around the
hematoma was increased, the number of neurons was decreased, nerve cell swelled, some cells showed pyknotic
necrosis, and the staining was deepened. The water content of the right base was increased significantly (P<0.05). The number of FJC positive and TUNEL positive cells around the
hematoma was increased significantly (P<0.05). The levels of NLRP3, ASC, caspase-1,
pro-caspase-1,
caspase-1/
pro-caspase-1 ratio, GSDMD-N, GSDMD, GSDMD-N/GSDMD ratio, IL-1β and
IL-18 were increased significantly (P<0.01, P< 0.05). Compared with ICH group, the percentage of successful placement of left forelimb and left turn was increased significantly in
MCC950 group (P<0.05), while the mNSS score and the volume of
hematoma were decreased significantly (P<0.01), the swelling degree of nerve cells around the
hematoma was reduced significantly, and the number of pyrotic necrotic cells was decreased. The water content of the right base was decreased significantly (P<0.05), and the number of FJC positive and TUNEL positive cells around the
hematoma was decreased significantly (P<0.05). The levels of NLRP3, ASC, caspase-1,
pro-caspase-1,
caspase-1/
pro-caspase-1 ratio, GSDMD-N, GSDMD, GSDMD-N/GSDMD ratio, IL-1β and
IL-18 were decreased significantly (P<0.05). Conclusion:
MCC950 can ameliorate nerve injury after ICH by inhibiting NLRP3
inflammasome mediated
inflammation and pyroptosis.