1.Effects of different mean arterial pressure levels on hemodynamics, tissue perfusion and oxygen metabolism in elderly patients with septic shock
Maoqin LI ; Jiyuan XU ; Jiaqiong LI ; Yanjun XU ; Xun MO ; Fei LU ; Lin LI ; Zhou ZHANG ; Songmei LI ; Huimin WANG
Chinese Journal of Geriatrics 2008;27(11):821-823
ObjectiveTo observe the effects of norepinephrine and dobutamine (NE+Dobu) on hemodynamics, tissue perfusion and oxygen metabolism in elderly patients with septic shock at different levels of mean arterial pressure (MAP). MethodsAfter aggressive fluid resuscitation,norepinephrine and dobutamine were administered in 18 elderly patients with septic shock to correct hypotension. The rate of dobutamine infusion was 5 ug. kg<'-1>. min<'-1> Norepinephrine was titrated to maintain MAP at levels of 65 mm Hg, 75 mm Hg and 85 mmHg. Four hours later, the changes of hemodynamics, oxygenation index, blood lactate, renal function and gastric pCO<,2> at every MAP level were observed. ResultsThere were no significant differences in heart rate (HR), pulmonary arterial wedge pressure (PAWP), volume of oxygen (VO<,2>), Blood lactate, pH value, △pCO<'2> and creatinine clearance rate (CCr) among the MAP levels of 65 mm Hg, 75 mm Hg and 85 mm Hg ( all P>0.05). Compared with MAP 65 mm Hg, cardiac index (CI), systemic vascular resistance index (SVRI), oxygen delivery over oxygen extraction ratio were obviously higher at MAP 75 mm Hg and 85 mm Hg [4.7±0.6, 5.1±0.7 vs. 4.0±0.6; 1162±278, 1276±319 vs. 1011±225; (697±53) ml. min<'1>. m<'2>,(711±68)ml. min<'-1>. m<'2> vs. (634±70) ml · min<'-1> · m<'2>; (0.28±0.02)%,(0.27±0.02)% vs. (0.25±0.02) %, respectively, all P<0.05). The urinary output at MAP levels of 65 mm Hg, 75 mm Hg and 85 mm Hg were (98±43)ml/h, (91±54) ml/h and(74±49)ml/h repectively, and only the differences between MAP 75 mm Hg and MAP 65 mm Hg had statistical significance (P<0.05).ConclusionsAfter aggressive fluid resuscitation, hemodynamics and renal function are improved at MAP 75 mm Hg after administration of norepinephrine and dobutamine in elderly patients with septic shock. It should be considered that MAP is appropriately increased in elderly patients with septic shock.
2. Effects of PSMB5 on proliferation and bortezomib chemo-resistance in human myeloma cells and its related molecular mechanisms
Huimin MO ; Qingyun WU ; Danyang HAN ; Rui LIU ; Xun MA ; Ping ZHOU ; Kailin XU
Chinese Journal of Hematology 2017;38(12):1053-1057
Objective:
To investigate the effects of proteasome beta 5 subunit (PSMB5) on proliferation and bortezomib (BTZ) chemo-sensitivity of multiple myeloma (MM) and its related molecular mechanisms.
Methods:
We used two MM cell lines, RPMI 8226 and BTZ drug-resistant cell line RPMI 8226/BTZ100 (hereinafter referred to as BTZ100) , as the research object. PSMB5 was overexpressed or knocked down in two myeloma cell lines via lentivirus transfection. CCK8 assay was used to detect the impact of PSMB5 on cell viability and bortezomib sensitivity in human myeloma cells; Using flow cytometry to test the effects of PSMB5 on apoptosis rate of human myeloma cells under the treatment of bortezomib; Apoptosis-related gene expression of Bax, Bcl-2, p-Akt and cleaved caspase-3 were detected by Western blot.
Results:
①PSMB5 overexpression and knockdown were successfully constructed in RPMI 8226 and BTZ100 cells. ②PSMB5 expression was positively correlated with cell proliferation of RPMI 8226 and BTZ100 cells (
3.Study on RAD51 Gene Regulatory Mechanism of Apigenin Affecting Cisplatin Sensitivity to NSCLC A 549 Cells
Lin MO ; Xin LIU ; Huimin YANG ; Xinrong HE ; Xiaolin WANG ; Chunhong TANG
China Pharmacy 2020;31(6):708-714
OBJECTIVE:To study the effects and mechanism o f apigenin on cisplatin sensitivity of NSCLC A 549 cells by regulating RAD51 gene. METHODS :Human lung cancer cisplatin-resistant cells A 549/DDP were selected and divided into control group(blank culture medium ),cisplatin group (5 g/L),apigenin low-dose and high-dose groups (10,20 μmol/L). MTT assay was used to detect the growth of A 549/DDP cells ,while the Annexin Ⅴ/PI double staining combined with flow cytometry were used to detect the apoptosis. A 549/DDP cells were collected and divided into cisplatin alone group (1,2,4,8,16 μg/mL), apigenin combination group (10 μmol/L,based on cisplatin ). MTT method was used to determine and calculate inhibitory rate of cell proliferation. IC 50 values of drugs were calculated by regression model ,and reversion index of apigenin was calculated. 18 nude mice were randomly divided into control group ,cisplatin alone group and apigenin combination group ,with 6 mice in each group. After A 549/DDP cells were inoculated to form the transplanted tumor ,normal saline ,cisplatin(2 mg/kg,once every other day ), cisplatin(the same dosage and usage )+apigenin solution (30 mg/kg,once a day )were injected intraperitoneally respectively. After 18 days of continuous administration ,the body weight of mice and the mass of the transplanted tumor were detected and the tumor inhibition rate was calculated. Human lung cancer cells A 549 and A 549/DDP were collected and divided into normal group (A549 cells),control group (A549/DDP cells ),cisplatin group (5 g/L,A549/DDP cells )and apigenin low-dose and high-dose groups (10,20 μmol/L,A549/DDP cells ),respectively. mRNA and protein expression of RAD51 were detected by real-time fluorescence quantitative PCR and Western blotting assay. RESULTS : Δ 基金项目:四川省教育厅(自筹经费)科研项目(No.12ZB227) *讲师,硕士。研究方向:肿瘤病理。E-mail:molin212@163.com Compared with control group ,the cell growth of apigenin # 通信作者:副教授,硕士生导师,硕士。研究方向:肿瘤病理。 low-dose and high-dose groups were decreased significantly , E-mail:xinrongH292@163.com apoptosis rates of them w ere increased significantly and higher ·708· China Pharmacy 2020Vol. 31 No. 6 中国药房 2020年第31卷第6期 than those of cisplat in group (P<0.05 or P<0.01). After combined with apigenin ,proliferation inhibition rate of A 549/DDP cells was increased significantly ,compared with cisplatin alone group with the same concentration (P<0.05). The IC 50 in the apigenin combination group was (5.81±0.47)μg/mL,significantly lower than (14.44±0.52)μg/mL in cisplatin alone group(P<0.05),and reversal index of apigenin was 2.49. The results of nude mice tumor inhibition experiment showed that after combined with apigenin,tumor inhibition rate of A 549/DDP bearing nude mice was 68.72%,significantly lower than 33.82% in cisplatin alone group. Compared with A 549 cells of normal group ,relative expression of RAD51 mRNA and protein were increased significantly in A549/DDP cells of control group (P<0.05). Compared with A 549/DDP cells of control group ,relative expression of RAD51 mRNA and protein in A 549/DDP cells were decreased significantly in apigenin low-dose and high-dose groups (P<0.05). Compared with cisplatin group ,relative expression of RAD51 mRNA and protein in A 549/DDP cells of apigenin low-dose and high-dose group were decreased significantly (P<0.05). CONCLUSIONS :Apigenin can effectively reverse drug resistance of cisplatin-resistant A 549/DDP cells in human lung cancer. The mechanism may be related to the reduction of RAD51 gene transcription and protein expression.