Effects of Puerarin on Hypoxia Induced Pyroptosis of Pulmonary Artery Smooth Muscle Cells Based on NLRP 3 Inflammasome / 中国药房

OBJECTIVE：To investigate the effects and mechanism of puerarin （Pue） on hypoxia-induced pyroptosis of pulmonary artery smooth muscle cells （PASMCs）. METHODS ：PASMCs of rats as research objects were randomly divided into normoxia group ，hypoxia group and hypoxia+Pue group （0.2 mmol/L）. Except for normoxia group ，other groups were cultured with 5％ CO2 and 3％ O2 at 37 ℃ for 24 hours to establish hypoxia model. Western blot assay was used to detect the expression of pyroptosis related proteins [NOD-like receptor protein- 3 （NLPR3），caspase-1，interleukin-1 β （IL-1 β），apoptosis-associated speck-like protein （ASC）]. Lactate dehydrogenase （LDH）release assay was used to detect the release of LDH in cells ；Hoechst 33342/PI double staining test was adopted to detect the proportion of pyroptosis positive cells. PASMCs was randomly divided into normoxia group+control plasmid group ，hypoxia+control plasmid group ，hypoxia+over-expression plasmid group and hypoxia+ over-expression plasmid+Pue group. Except for the normoxia+control plasmid group ，the other groups were established hypoxia model by the same method. After transfection of control plasmid or NLRP 3 over-expression plasmid ，Western blot ，LDH release test and Hoechst 33342/PI double staining test were used to investigate whether Pue could inhibit hypoxia-induced PASMCs pyroptosis by interfering with the activity of NLRP 3 inflammasomes. RESULTS ：Compared with normoxia group ，the expression of pyroptosis related proteins ，the release of LDH and the proportion of pyroptosis positive cells were increased significantly in hypoxia group （P＜0.05 or P＜0.01）. Pue had the effect of reversing the above indexes （P＜0.05 or P＜0.01）. When the NLRP 3 inflammasome was over-expressed ，the expression of pyroptosis related proteins ，the release of LDH and the proportion of Δ 基金项目：黑龙江省自然科学基金资助项目（No.ZD201416） pyroptosis positive cells were increased significantly （P＜0.05 ＊教授，博士生导师 ，博士。研究方向 ：心血管药理学 。电话： or P＜0.01）. Pue could inhibit the above phenomenon through 0451-58853046。E-mail：zhangxd85@163.com regulating NLRP 3 inflammasome （P＜0.05 or P＜0.01）. 中国药房 2021年第32卷第11期 China Pharmacy 2021Vol. 32 No. 11 ·1337· CONCLUSIONS：Pue can significantly inhibit the hypoxia-induced pyroptosis of PASMCs by down-regulating the expression of pyroptosis related proteins ，reducing the release of LDH and proportion of pyroptosis positive cells. The mechanism is related to the activity inhibition of NLRP 3 inflammasome.

Primary immunodeficiency associated hemophagocytic lympohistiocytosis / 国际儿科学杂志

Hemophagocytic lymphohistiocytosis (HLH) is classified into primary and secondary HLH according to the etiology.Primary HLH includes familial HLH and primary immunodeficiency HLH.Primary immunodeficiency HLH includes Chediak-higashi syndrome,Griscelli syndrome Ⅱ,Hermansky-Pudlak syndrome Ⅱ,X-linked lymphoproliferative syndrome I,X-linked lymphoproliferative syndrome Ⅱ and so on.These diseases may develop into HLH because of mutations in genes resulting in impaired function of natural killer cells and T cells,macrophage activation and extreme inflammation.The common clinical manifestations are repeated infection,prolonged fever,hepatosplenomegaly,cytopenia,hemophagocytosis in bone marrow,elevated ferritin,low fibrinogen and so on.The immunochemotherapy of dexamethasone,etoposide,cyclosporine A can be an effective remission-inducing treatment.Hematopoietic stem cell transplantation is the only known cure of the primary immunodeficiency HLH.