Comparative study of domestic and imported bilobalide in the treatment of Pneumocystis carinii pneumonia in rats - Master's thesis - Dissertation

Pneumocystis carinii pneumonia (PCP) is a common infection among individuals with weakened immune systems, such as cancer patients undergoing chemotherapy, organ transplant recipients on immunosuppressants, and those with autoimmune disorders or acquired immunodeficiency. The condition became more prevalent during the first AIDS epidemic in 1984, as the number of at-risk individuals increased significantly. Currently, the primary treatments include sulfamethoxazole (TMP-SMZ) and pentamidine, but these drugs often lead to severe side effects or resistance, making the search for new treatment options crucial.

Studies have shown that Ginkgolide may offer some therapeutic benefits against PCP [1]. This research compares the effectiveness of domestically produced and imported Ginkgolide in treating this condition, and the findings are presented below.

Materials and Methods

1. Establishment of PCP Model

A total of 70 female Wistar rats, weighing between 230-270 grams, were obtained from the Chongqing Medical Science Experimental Animal Center (license number: Sichuan Medical Laboratory Animal Management Committee, No. 2 4301045). The experimental model of pneumocystis pneumonia was established according to a previously published method [1].

2. Grouping and Treatment

The PCP-infected rats were randomly divided into four groups, with 16 rats per group. Group A served as the control group, receiving no treatment. Group B received domestic Ginkgolide (Guizhou Aofang Biotechnology Co., Ltd., batch number 010405, 95% HPLC, powder) via intraperitoneal injection at a dose of 20 mg/kg/day for 8 days. Group C received imported Ginkgolide (Sigma, batch 053K1397, 95% HPLC, powder) under the same conditions. Group D was treated with a combination of sulfamethoxazole (Southwest Pharmaceutical Co., Ltd., batch number 020503, SMZ: TMP = 5:1, tablet) at 100 mg/kg/day and trimethoprim at 20 mg/kg/day for 8 days. After an 8-day treatment period, the drug was discontinued for one week, and efficacy was evaluated at the end of the ninth week.

3. Efficacy Evaluation

During the experiment, the survival status of each group was closely monitored, and body weight was recorded weekly. At the end of the study, the lungs, trachea, and hilar tissues were removed, dried, and weighed. Each lung was cut into sections, mounted on slides, stained with GMS, and examined under oil immersion. A total of 100 fields per lung section were observed, and the number of Pneumocystis cysts was counted. The average number of cysts per field and per rat was calculated for each group.

4. Statistical Analysis

The body weight, lung weight, and lung-to-body weight ratio of the rats in each group were compared using ANOVA. The reduction rate of cysts was calculated using the following formula:

1. Results

1.1 Survival Status

At the end of the experiment, two rats died in Group A, one in Group C, while no deaths occurred in Groups B and D.

1.2 Body Weight Changes

The average body weight of rats in Group A decreased, whereas the other treatment groups showed varying degrees of weight gain. Statistical analysis revealed significant differences in body weight between Group A and the other groups (P < 0.05). There was no significant difference between the domestic and imported Ginkgolide groups (P > 0.05).

1.3 Lung Weight and Lung-to-Body Weight Ratio

The lung weight and lung-to-body weight ratio in Group A were significantly higher than in the treatment groups (P < 0.05). No significant differences were found between the domestic and imported Ginkgolide groups (P > 0.05).

1.4 Cyst Count in Lung Prints

The average number of cysts per field in the treatment groups was lower than that in the control group. These results suggest that both domestic and imported Ginkgolide show promising effects in reducing Pneumocystis infections in rats.