Successful use of plasma exchange in fulminant lupus myocarditis coexisting with pneumonia: A case report.

BACKGROUND: Fulminant lupus myocarditis is a rare but fatal manifestation of systemic lupus erythematosus. Aggressive immunosuppressive treatments are important in its successful management. However, they can significantly damage the immunity and are associated with a considerable risk of infection development and spread. We present a rare and complicated case of a 20-year-old female diagnosed with fulminant lupus myocarditis accompanied by pneumonia. The patient was successfully treated with plasma exchange (PE) for fulminant lupus myocarditis. CASE SUMMARY: A 20-year-old Chinese woman presented to the Hematology Department complaining of fatigue and knee pain. Blood test showed anemia and thrombocytopenia. On the second day of hospitalization, she was transferred to the ICU due to dyspnea and hypotension. Autoimmune profiles showed hypocomplementemia and positive antinuclear antibodies. Computer tomography showed an enlarged heart and pneumonia. Ultrasound revealed an enlarged heart with a low left ventricular ejection fraction. Fulminant lupus myocarditis with cardiogenic shock was initially considered. Due to the accompanying pneumonia, aggressive immunosuppression was contraindicated. Her cardiac function remained critical after the initial therapy of intravenous immunoglobulin and corticosteroids at a conventional dose, but she responded well to later PE therapy plus corticosteroids administration. The patient fully recovered with normal cardiac function. CONCLUSION: This case indicates that PE is a valuable treatment choice without adverse effects of immunosuppression in patients with fulminant lupus myocarditis and coexisting infection.

miR­21­5p regulates type II alveolar epithelial cell apoptosis in hyperoxic acute lung injury.

Hyperoxia­induced acute lung injury (HALI) as one of the most common complications in patents on mechanical ventilation, and there are no efficient methods to overcome this at present. It was hypothesized that microRNA 21­5p(miR­21­5p) can promote the survival of type II alveolar epithelial cells (AECII), alleviating HALI. The present study aimed to combine gene chip analysis with the overexpression miR­21­5p to develop a novel therapeutic option for HALI. It was found that AECII apoptosis was an important pathogenic event in the development of HALI, and the overexpression of miR­21­5p prevented HALI, associated with reducing AECII apoptosis. These results were obtained using adenoviral/lentiviral vectors, which overexpressed miR­21­5p, to transfect AECII cells in vitro and in vivo. It was found that the overexpression of miR­21­5p reduced the apoptotic rate of the AECII cells. In addition, miR­21­5p decreased the ratio of B­cell lymphoma 2 (Bcl­2)­associated X protein/Bcl­2 and the expression of caspase­3. It was also revealed that the overexpression of miR­21­5p alleviated acute lung injury in adult rats exposed to a hyperoxic environment. These results suggest that miR­21­5p may become a novel therapeutic option for patients with HALI, by protecting AECII cells from apoptosis.

[Screening type II alveolar epithelial cell apoptosis related microRNA].

OBJECTIVE: To screen type II alveolar epithelial cell (AECII) apoptosis related microRNA (miRNA) with gene chip technology, provide a new strategy for the prevention and treatment of hyperoxia-induced acute lung injury(HALI). METHODS: AECII of male Sprague-Dawley (SD) rats was primarily cultured for 36 hours, then exposed to 0.5 mmol/L H2O2 to establish apoptosis model. Transmission electron microscope (TEM) was used to identify AECII and to observe apoptosis cell morphology. Before and after H2O2 injury for 2.5, 6, 12 and 24 hours, fluorescence-activated cell sorting (FACS) was employed to detect apoptosis rate. Additionally, gene chip technology and real time polymerase chain reaction (RT-PCR) were used to screen and verify apoptosis related miRNA respectively. RESULTS: Microvilli and osmiophilic multilamellar body were found under TEM, which were the characteristic structure of AECII. This proved that the cells cultured were AECII. After H2O2 injury for 24 hours, cytoplasmic retraction, chromatin condensation and margination, microvilli and osmiophilic multilamellar body disappearance could be found under TEM. Compared with the blank control group, the apoptosis rate of AECII was significantly increased after exposed to 0.5 mmol/L H2O2, and gradually increased with time [the early apoptosis rate before and after H2O2 injury for 2.5, 6, 12 and 24 hours were (9.43±1.02)%, (18.38±2.91)%, (28.57±1.18)%, (35.83±2.66)% and (57.68±2.22)%, respectively, all P<0.05]. Compared with before H2O2 injury, cells at 24 hours accompanied a significantly changed miRNA expression profiling, in which apoptosis related miRNA had been screened, they were rno-miR-449a-5p, rno-miR-34b/c-5p, rno-miR-200a/c-3p, rno-miR-146a-5p, rno-miR-141-3p, rno-miR-21-5p, rno-miR-375-3p, rno-miR-29b-3p, rno-miR-214-5p, rno-miR-210-5p and rno-miR-214-3p,and the results of RT-PCR were consistent with the gene chip results. CONCLUSIONS: Screened out AECII apoptosis related miRNA, and miR-34 family may play a key role in AECII apoptosis regulation. Rno-miR-21-5p may be an important anti-apoptotic gene in AECII apoptosis regulation.

[The effect of heme oxygenase-1 on apoptosis and aquaporin-1 expression in type II primary alveolar epithelial cells in rat].

OBJECTIVE: To explore the effect of heme oxygenase-1 (HO-1) on apoptosis and expression of aquaporin-1 (AQP-1) in primary type II alveolar epithelial cells (AECII) in rats with hydrogen peroxide (H2O2) induced oxidative damage. METHODS: Lung tissue of male Sprague-Dawley (SD) rats was collected. Primary AECII were isolated, purified, and cultured for 24 hours, then they were divided into four groups: (1) normal group (treated with normal saline); (2) H2O2 injury group (treated with H2O2 0.5 mmol/L); (3) HO-1 control group (treated with HO-1 1 µmol/L); (4) HO-1 protection group (treated with HO-1 1 µmol/L and H2O2 0.5 mmol/L). Cells of each group were cultured for 12 hours after various treatment. The cell suspension was collected before and 1, 3, 6, 12 hours after treatment, the expression of AQP-1 was determined by Western blotting and the apoptosis rate was assessed with flow cytometer. RESULTS: The expression of AQP-1 in H2O2 injury group was significantly declined with time, and was lower than that in normal group at each time point after treatment. The expression of AQP-1 in HO-1 control group and HO-1 protection group was significantly increased with time, and was higher than that of other groups at each time point after treatment. The expression of AQP-1 in HO-1 protection group was significantly up-regulated compared with that in H2O2 injury group (1 hour: 60.81 ± 5.78 vs. 46.21 ± 4.81, 3 hours: 63.05 ± 9.61 vs. 39.32 ± 4.96, 6 hours: 92.59 ± 8.21 vs. 36.82 ± 4.32, 12 hours: 86.16 ± 14.84 vs. 34.88 ± 2.66, all P<0.05). No significant difference in apoptosis rate was found between normal group and HO-1 control group. The apoptosis rate in H2O2 injury group was increased with time, and was significantly higher than that of normal group at each time point. The apoptosis rate in HO-1 protection group was gradually increased within 3 hours after treatment, then decreased and remained stable after 6 hours, while it was significantly lower than that of H2O2 injury group at each time point [1 hour: (9.04 ± 2.17)% vs. (15.14 ± 2.47)%, 3 hours: (12.90 ± 2.04)% vs. (22.37 ± 4.84)%, 6 hours: (10.42 ± 1.68)% vs. (27.83 ± 3.93)%, 12 hours: (11.97 ± 1.91)% vs. (33.63 ± 6.61)%, all P<0.05]. A negative correlation was found between AQP-1 and apoptosis rate in H2O2 injury group (r=-0.723, P<0.001), and a regression correlation was found [y=672.548(0.914) (x), R²=0.597]. AQP-1 was not correlated with apoptosis rate in HO-1 protection group (r=0.210, P=0.193), but a regression correlation was found [y=e((3.130 - 59.654/x )), R²=0.225]. CONCLUSIONS: HO-1 could increase the expression of AQP-1 in H2O2 injured AECII of rat, and lower its apoptosis rate. Increase in the expression of AQP-1 may be the underlying mechanism of anti-oxygenation property of HO-1.